Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
The DELIVER-MS study seeks to answer the important question: Does early treatment with highly effective DMT improve the prognosis for people with MS? This is an area of significant controversy and no data currently exist to guide treatment choices for patients and clinicians. The study results will help guide overall treatment philosophy and will be applicable not only to a wide range of existing therapies but also to new therapies, meeting a significant
unmet need in patient decision making and aiding the decision for medication approval by third parties.
William Schmalstieg
All
18 Years to 60 Years old
Phase 4
This study is NOT accepting healthy volunteers
STUDY00004712
STUDY00004712
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Inclusion Criteria:
Men and women aged 18 to 60 years.
Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
RRMS disease course as defined by the 2013 revisions of the MS clinical course definition (4).
Participants must have evidence of active disease based on: one or more MS relapses within the last 18 months prior to screening visit or radiological evidence of MS activity (≥2 new T2 lesions within the last 12 months from screening [compared to a previous recent MRI within 18 months of screening] or ≥1 GdE demonstrated on brain or spinal cord MRI performed within the last 12 months of screening).
Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS DMT at any time in the past).
Participants must be eligible to receive at least one form of DMT within each treatment arm.
EDSS at Baseline visit ≤ 6.5
Exclusion Criteria:
Participants with contraindications to all forms of DMT in either of the treatment arms.
Participants must never have received any of the following medications: natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine, siponimod, interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, daclizumab, mitoxantrone, diroximel fumarate, ozanimod, monomethyl fumarate, ponesimod.
Participants must have not received any of the following medications, for reasons other than MS, in the last 12 months: cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, leflunomide, laquinimod, atacicept, other monoclonal antibodies.
Participants with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study
Participants unable to provide informed consent.
Contraindication or inability to undergo MRI with Gd due to metal or metal implants, allergy to Gd contrast, claustrophobia, pain, spasticity, or excessive movement related to tremor.
Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the PI, is likely to affect the participant's ability to comply with the study protocol.
Early Highly Effective Therapies Group, Escalation Therapies Group, Early Highly Effective Therapies Group, Escalation Therapies Group
Are you planning to receive the yellow fever vaccine for upcoming travel? This study may be for you!
How well a vaccine works sometimes varies by geography, with good protection in one part of the world and poor protection in others. In this research study, the research team is investigating if this is due to different infections in communities, which could affect parts of the immune system that are needed for a good response to a vaccine.
Healthy participants who receive the yellow fever vaccine in Uganda and Minnesota will have their levels of infections (from viruses, bacteria, fungi, parasites, and helminths [a type of parasitic worm])
compared. This will help us learn more about relationships between these infections, how they affect immune systems, and how that affects the body’s response to a vaccine.
Timothy Schacker
All
18 Years to 60 Years old
Phase 1/Phase 2
This study is also accepting healthy volunteers
STUDY00004946
STUDY00004946
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Inclusion Criteria:
No contraindication to Yellow Fever vaccine (immunosuppressed for any reason or on an immunosuppressive drug where a live virus vaccine is contraindicated).
If female of childbearing age must agree to contraception for one month following administration of the vaccination.
Exclusion Criteria:
History of yellow fever or previous vaccination for yellow fever
Known bleeding disorder
Prior surgery complicated by clotting abnormality
Psychiatric or behavioral disorder that, in the opinion of the investigator, will make it difficult for the participant to complete the study
History of acute hypersensitivity reaction to any component of the vaccine (including gelatin, eggs, egg products, or chicken protein).
Thymus disorder associated with abnormal immune function
Immunosuppression from any of the following: HIV infection or AIDS, malignant neoplasms, primary immunodeficiencies, transplantation, transplantation, immunosuppressive or immunomodulatory therapy (corticosteroids, alkylating agents, antimetabolites, TNF inhibitors, IL-1 blocking agents, monoclonal antibodies targeting immune cells), previous radiation therapy.
Pregnant or breastfeeding at the time of vaccination.
Planning to conceive within 28 days of enrollment and vaccination with the yellow fever vaccine.
The purpose of this study is to find out if using a computer program (called iDose) to guide infliximab dosing is more effective and safer than using standard infliximab dosing over 52 weeks. All patients in this study will be receiving infliximab as part of their medical care, this study is only looking at two different methods of determining the dose and timing of administration.
Byron Vaughn
Male or Female
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
STUDY00013632
STUDY00013632
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Inclusion Criteria:
Males or nonpregnant, nonlactating females aged 16 to 80 years inclusive.
Diagnosis of CD prior to screening using standard endoscopic, histologic, or radiologic criteria. Subjects with patchy colonic inflammation initially diagnosed as indeterminate colitis would meet inclusion criteria, if the investigator feels that the findings are consistent with CD.
Moderately to severely active CD, defined by a total Crohn's Disease Activity Index (CDAI) score between 220 and 450 points, and at least 1 of the following:
Elevated CRP > upper limit of normal )
Elevated fecal calprotectin (FC) (> 250 μg/g)
SES-CD > 6, or SES-CD > 3 for isolated ileal disease
Physician intends to prescribe IFX as part of the usual care of the subject.
No previous use of IFX prior to enrolment in the current study, unless the participant received 1 prior dose of IFX (within 2.5 weeks of enrolment) and met all eligibility criteria at the time of starting IFX and IFX was administered according to the requirements outlined in this protocol
Able to participate fully in all aspects of this clinical trial.
Written informed consent must be obtained and documented.
Exclusion Criteria:
Subjects with any of the following CD-related complications:
Abdominal or pelvic abscess, including perianal
Presence of stoma or ostomy
Isolated perianal disease
Obstructive disease, such as obstructive stricture
Short gut syndrome
Toxic megacolon or any other complications that might require surgery, or any other manifestation that precludes or confounds the assessment of disease activity (CDAI or SES-CD)
Total colectomy.
History or current diagnosis of ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
Current bacterial or parasitic pathogenic enteric infection, according to SOC assessments, including: Clostridioides difficile; tuberculosis; known infection with hepatitis B or C virus; known infection with HIV; sepsis; abscesses. History of the following: opportunistic infection within 6 months prior to screening; any infection requiring antimicrobial therapy within 2 weeks prior to screening; more than 1 episode of herpes zoster or any episode of disseminated zoster; any other infection requiring hospitalization or intravenous antimicrobial therapy within 4 weeks prior to screening.
Has any malignancy or lymphoproliferative disorder other than nonmelanoma cutaneous malignancies or cervical carcinoma in situ that has been treated with no evidence of recurrence within the last 5 years.
Known primary or secondary immunodeficiency.
PNR to adalimumab, defined as no objective evidence of clinical benefit after 14 weeks of therapy.
Subjects with failure to a prior biologic, defined as PNR or SLR, will be excluded when a maximum of 40% of the planned enrollment (approximately 78 subjects) have failure to prior biologic exposure.
Concomitant use of oral corticosteroid therapy exceeding prednisone 40 mg/day, budesonide 9 mg/day, or equivalent, unless a tapering schedule is initiated with a plan to be off CS by Week 14
Presence of any medical condition or use of any medication that is a contraindication for IFX use, as outlined on the product label.
A concurrent clinically significant, serious, unstable, or uncontrolled underlying cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound the study results, pose additional risk to the subject, or interfere with the subject's ability to participate fully in the study.
Pregnant or lactating women, to be excluded based on the physician's usual practice for determining pregnancy or lactation status.
Known intolerance or hypersensitivity to IFX or other murine proteins.
The clinical investigation objective is to study the safety and efficacy of an anti-platelet-free antithrombotic regimen in patients with advanced heart failure treated with the HM3 LVAS.
Rebecca Cogswell
All
18 Years to old
N/A
This study is NOT accepting healthy volunteers
STUDY00009255
STUDY00009255
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Inclusion Criteria:
Subject will receive the HeartMate 3 per standard of care (SOC) in accordance with the approved indications for use in the country of implant.
Subject will receive the HeartMate 3 as their first durable VAD.
Subject must provide written informed consent prior to any clinical investigation related procedure.
In female patients of child bearing capability, subject will not be currently pregnant or breastfeeding and on appropriate contraception.
Exclusion Criteria:
Post-implant additional temporary or permanent mechanical circulatory support (MCS).
Investigator mandated antiplatelet therapy for other conditions (including mandated presence or absence of antiplatelet agent).
Patients who are nil per os (NPO) post-implant through day 7.
Subjects with a known allergy to acetylsalicylic acid (aspirin).
Participation in any other clinical investigation(s) involving an MCS device, or interventional investigation(s) likely to confound study results or affect study outcome.
Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
To compare the outcomes of patients with complex lesions treated with imaging guidance with IVUS versus angiography only.
Ganesh Raveendran
All
18 Years to old
N/A
This study is NOT accepting healthy volunteers
STUDY00014771
STUDY00014771
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Inclusion Criteria:
Age ≥ 18 years at screening
PCI with stent implantation involving a high risk or complex lesion defined as involving at least one of the following characteristics:
Chronic total occlusion
In-stent restenosis
Severe coronary artery calcification
Long lesion (≥ 28 mm in length)
Bifurcation lesion (Any Medina class that involves main branch disease with a side branch ≥2.0 mm)
Stable angina, unstable angina, or non-ST Elevation myocardial infarction (NSTEMI), undergoing PCI of a single or multivessel coronary artery stenosis
PCI performed with either angiography alone, or IVUS guidance used
Exclusion Criteria:
Subjects with acute ST elevation myocardial infarction (STEMI), or cardiogenic shock
Use of fibrinolytic therapy within 24 hours of PCI
Planned revascularization as a staged procedure
Stent thrombosis
Use of optical coherence tomography (OCT) during the index procedure
Eagle Eye Platinum digital IVUS catheter with optional SyncVision, Resolute Onyx Drug Eluting Stent, Eagle Eye Platinum digital IVUS catheter with optional SyncVision, Resolute Onyx Drug Eluting Stent
This is an open-label single arm trial of letermovir (LTV, Prevymis) for prevention of recurrent CMV infection in allogeneic hematopoietic cell transplantation (HCT) recipients with history of
CMV infection. The study is being conducted at MSKCC and at the University of Minnesota.
Thirty-six HCT recipients who are ≥12 years of age, had clinically significant CMV infection
treated with CMV antivirals and are at high risk for recurrent CMV infection, defined as
receiving a transplant from an HLA mismatched donor (including cord blood), acute or chronic graft versus host disease (GVHD) requiring either topical and/or systemic steroid treatment within 14 days prior to enrollment, or T cell-depleted (CD34+-selected) allograft, will be eligible to participate in the study.
Jo-Anne Young, MD
All
12 Years to old
Phase 2
This study is NOT accepting healthy volunteers
STUDY00011646
STUDY00011646
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Inclusion Criteria:
Age >/= 12 years (any weight)
Have received allogenic HCT
Have received preemptive therapy for clinically significant CMV infection post-HCT and have completed preemptive therapy no longer than 7 days prior to enrollment. Preemptive treatment includes ganciclovir, valganciclovir, foscarnet or cidofovir. Clinically significant CMV infection is defined as CMV viremia requiring preemptive therapy or CMV EOD. Patients who have received LTV prophylaxis prior to onset of clinically significant CMV infection prior to enrollment (see also exclusion criteria below).
Have one or more risk factors for recurrent CMV infection:
Human leukocyte antigen (HLA) mismatch
HLA-related (sibling) donor with at least one mismatch at the HLA-A, -B or -DR gene loci
Haploidentical donor
Unrelated donor with at least one mismatch at the HLA-A, -B, -C or -DRC1gene loci, or
Cord blood as stem cell source
Acute or chronic GVHD requiring either topical steroids for gastrointestinal GVHD and/or systemic steroid treatment (>/= 1mg/kg/day of prednisone or equivalent dose of another corticosteroid) within 14 days prior to enrollment
T-cell-depleted allograft ex-vivo or in-vivo T-cell depleting agents including but not limited to ATG, alemtuzimab and post HCT cyclophosphamide.
For adult patients, able to provide written consent and complete the informed consent. For patients under 18 years, the patient's parent(s) or legal guardian(s) must provide informed consent and the patient must provide written assent to participation in the study.
Willing and able to comply with trial instructions and requirements
Male and female patients of childbearing potential must be willing to use a highly effective method of contraception for the course of the study. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
Subject eligibility criteria for the observational cohort:
Age 18 years or older
First allogenic peripheral blood or marrow HCT
LTV prophylaxis starting <30 days post HCT and given for at least 6 weeks
Exclusion Criteria:
Clinically significant CMV infection present at enrollment
Breakthrough CMV infection while on primary LTV prophylaxis (unless patient non-adherent or unable to adequately absorb letermovir or documented resistance to LTV.
Glomerular filtration rate (GFR) = mL/min/1.73m^2(equivalent to creatinine clearance =10 mL/min)
Severe hepatic impairment
Routine use of high-dose acyclovir (doses of > 800 mg twice daily), valacyclovir (doses of > 500mg twice daily), or famciclovir (doses > 500mg/day) for varicella zoster virus (VZV)/herpes simplex virus prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration dose not exceed 14 days total. Short courses of IV cidofovir for adeno virus (ADV) are permissible
Suspected or known hypersensitivity to active or inactive ingredients of LTV formulations
Patients treated with a medication whose administration with LTV is ontraindicated and whose discontinuation is not possible. Contraindicated medications include pimozide, ergot alkaloids and pitavastatin or simvastatin when co-administered with cyclosporine.
Imminent demise (expected survival <6 weeks)
Documented positive result for human immunodeficiency virus antibody (HIV-Ab) or for hepatitis C virus antibody (HCV-Ab) with detectable HCV RNA, or hepatitis B surface antigen (HBsAg) at any time prior to HCT
Need for mechanical ventilation and/or vasopressor support at the time of enrollment
Pregnancy or breastfeeding
Plans to conceive or father children within the projected duration of the trial
History of current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would place the subject at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study.
The following antivirals are allowed up to the listed dose limits:
Acyclovir up to 800 mg twice daily
Valacyclovir up to 500 mg twice daily
Famciclovir up to 500 mg/day for VZV/HSV prophylaxis; limited treatment courses at higher doses for VZV infections are permissible if treatment duration does not exceed 14 days total.
Short courses of IV cidofovir for ADV (up to two doses)
Exclusion criteria for observational cohort:
Clinically significant CMV infection during the 100 days following HCT. Clinically significant CMV infection defined as either CMV viremia requiring preemptive therapy with CMV antivirals or CMV end organ disease (EOD)
Grade 3-4 GVHD
Cord blood as cell source for HCT
Treatment with systemic steroids (>0.5mg/kg for 2 weeks or longer) within 3 weeks prior to enrollment
The purpose of this study is to better understand how tobacco and nicotine products affect our bodies. In this observational study smokers, vapers, smokeless tobacco users, nicotine replacement product users, non-users, and ex-users will be asked to provide biological samples. We will look for biological “markers” (biomarkers), or chemical changes in the body, that occur due to tobacco or nicotine exposure. Collected samples will be used for the development of biomarkers of toxicant exposure and for assessing exposure between the different groups. The intent is to eventually use these biomarkers to improve detection, prevention, and treatment strategies for tobacco-related diseases.
This study will allow us to test currently used biomarkers, and to establish a biorepository (sample bank) to identify and develop new biomarkers associated with tobacco exposure and cessation.
The type of samples and amount collected will depend on the specific biomarker(s) being developed or tested. Potential samples include saliva, cheek (buccal) & oral cells, blood, urine, hair, and/or nail clippings.
Stephen Hecht, PhD
Male or Female
18 Years and over
This study is also accepting healthy volunteers
0908M70881
0908M70881
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Inclusion Criteria:
• 21 years or older
• Daily user of tobacco or nicotine products
The purpose of this trial is to evaluate the efficacy, safety, and
tolerability of BI 1015550 9 mg bid and 18 mg bid compared to
placebo in patients with IPF in addition to patient’s standard of care
over the course of at least 52 weeks.
New treatments with better tolerability are needed for patients with
IPF to further reduce the decline in lung function and improve
quality of life. Based on its anti-inflammatory and antifibrotic
properties and the preliminary clinical evidence described,
BI 1015550 may provide an additional treatment option to patients
with pulmonary fibrosis irrespective of concomitant treatment with
standard of care.
Hyun Kim
All
40 Years to old
Phase III
This study is NOT accepting healthy volunteers
STUDY00016653
STUDY00016653
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Inclusion criteria
Patients ≥40 years old at the time of signed informed consent.
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
Diagnosis of Idiopathic Pulmonary Fibrosis (IPF)
Patients may be either:
on a stable therapy* with nintedanib or pirfenidone for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. Combination of nintedanib plus pirfenidone is not allowed. (*stable therapy is defined as the individually and general tolerated regimen of either nintedanib or pirfenidone (no dose changes) for at least 12 weeks.)
not on a treatment with nintedanib or pirfenidone for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment.
Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1.
Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) corrected for Haemoglobin (Hb) [Visit 1] ≥25% and <90% predicted of normal at Visit 1.
Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control. Of note, oral hormonal contraceptives are not considered a highly effective method due to potential drug-drug interactions.
Exclusion criteria
Relevant airways obstruction (prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced vital capacity (FVC) <0.7) at Visit 1.
In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
Acute Idiopathic Pulmonary Fibrosis (IPF) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined).
Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not fully recovered according to investigator judgement within the 4 weeks prior to randomization (Visit 2).
Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery.
Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) >2.5 x Upper limit of normal (ULN) or total Bilirubin >1.5 x ULN at Visit 1.
Further exclusion criteria apply.
Specific Aims:
Specific Aim 1: Determine whether a three-month course of daily brivaracetam reduces below-level neuropathic pain in SCI. The objective of this aim is to assess efficacy of a three-month course of brivaracetam to reduce neuropathic pain in men and women with SCI. We will assess change in pain intensity and related outcomes, including mood, satisfaction with life, and community integration. We will monitor drug adverse events and tolerability.
Specific Aim 2: Determine whether a three-month course of daily brivaracetam increases parietal operculum brain connectivity. The objective of this exploratory aim is to assess the effect of a three-month course of brivaracetam treatment on parietal operculum activation and connectivity in SCI. We will assess changes in cortical activity of related pain perception regions and networks in the brain in response to brivaracetam treatment compared to placebo using rsfMRI and pain-related task-based fMRI. To achieve this aim, we will test the working hypothesis that brivaracetam increases parietal operculum activation and connectivity compared to placebo, using rsfMRI, task-based fMRI, and a validated image processing protocol. We will also examine changes in network connectivity and brain activity in the insula, because of its concurrent reported importance for neuropathic pain in SCI. We will assess the association between functional connectivity of the parietal operculum and the insula and change in pain intensity in response to brivaracetam treatment.
Specific Aim 3: Determine whether baseline microRNA-485 levels are associated with response to brivaracetam treatment. The objective of this exploratory aim is to assess microRNA expression as a potential predictive biomarker of response to brivaracetam treatment. To achieve this, we will test the working hypothesis that baseline circulating miR-485 levels predict change in pain intensity in response to brivaracetam treatment. To test this, we will use Next-Generation sequencing. We will assess miR-485 levels at baseline and after a three-month treatment course.
Ricardo Battaglino
All
18 Years to old
Phase 3
This study is NOT accepting healthy volunteers
STUDY00015302
STUDY00015302
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Inclusion Criteria:
18 years of age or older
Injured for > 3 months
Completed inpatient rehabilitation and living in the community
Chronic sublesional neuropathic pain defined as persistent pain (VAS grade 3-10) for three months or more
For people of child-bearing potential: currently practicing an effective form of two types of birth control (defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly).
Exclusion Criteria:
Progressive myelopathy secondary to posttraumatic cord tethering or syringomyelia
Active use of drugs known to interact with brivaracetam: rifampin, carbamazepine, sodium oxybate, buprenorphine, propoxyphene, levetiracetam, and phenytoin.
Brain injury or cognitive impairment limiting the ability to follow directions or provide informed consent
Pregnancy or lactation
Epilepsy or active treatment for seizure disorder
Past or current suicidality
Active treatment for psychiatric disease
Drug addiction
Moderate or heavy alcohol intake (up to four alcoholic drinks for men and three for women in any single day, and a maximum of 14 drinks for men and 7 drinks for women per week)
Hepatic cirrhosis, Child-Pugh grades A, B, and C
Impaired renal function (GFR<60ml/minute)
Contraindications to brivaracetam or pyrrolidine derivatives including allergy
Active clinically significant disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrine, psychiatric, hematologic, urologic, or other acute or chronic illness) that, in the opinion of the investigator, would make the patient an unsuitable candidate for this trial.
History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of brivaracetam
Use of any investigational drug 30 days prior to enrollment in this study
Enrollment in another clinical trial.
This Phase 3 study is being conducted to assess the long-term safety,
tolerability, and efficacy of sotatercept in PAH. Long-term followup
of patients receiving sotatercept is important to understand the
maintenance and durability of treatment effect (especially in the
presence of background PAH therapy) and to provide greater
opportunity for pharmacovigilance following sotatercept treatment in
the selected patient populations.
This LTFU study is supported by data from the PULSAR study
(Phase 2, NCT03496207), in which treatment with sotatercept
resulted in hemodynamic and functional improvements in the study
participants, including those receiving maximal PAH therapy with
double/triple drug combinations and intravenous prostacyclin.
Thenappan Thenappan
All
18 Years to old
Phase 3
This study is NOT accepting healthy volunteers
STUDY00016119
STUDY00016119
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Inclusion Criteria:
Participants must have completed their current respective PAH sotatercept clinical study and its requirements, and must not have discontinued early.
Participants must be willing to adhere to the study visit schedule and understand and comply with all protocol requirements.
Participants must have the ability to understand and provide documented informed consent.
Females of childbearing potential must:
Have a negative pregnancy test as verified by the investigator prior to starting study drug administration; she must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug.
If sexually active, have used, and agree to continue to use highly effective contraception in combination with a barrier method without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study drug.
Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug.
Male participants must:
Agree to use a condom, defined as a male latex condom or non latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy.
Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug.
Participants must agree not to participate in any other trials of investigational drugs/devices while they are enrolled in the A011-12 study.
Exclusion Criteria:
Not enrolled in a PAH parent study at the time of enrollment.
Missed more than the equivalent of 4 consecutive doses between the end of parent study and the start of this study.
Presence of an ongoing serious adverse event that occurred during a PAH sotatercept clinical study that is assessed to be possibly or probably related to sotatercept.
Pregnant or breastfeeding females.
This is a Prospective, open-label, non-inferiority, randomized controlled trial (1:1 randomization) with blinded end-point analysis comparing the use of Prednisone versus Prednisone plus Methatrexate in the treatment of Cardiac Sarcoidosis.
Chetan Shenoy
All
18 Years to old
Phase III
This study is NOT accepting healthy volunteers
STUDY00015181
STUDY00015181
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Inclusion Criteria:
(i) Cardiac sarcoidosis presenting with one or more of the following clinical findings:
advanced conduction system disease (defined as Mobitz II AV block or third degree AV block)
significant sinus node dysfunction (defined as average HR less than 40bpm when awake and/or sustained atrial arrhythmias)
non- sustained or sustained ventricular arrhythmia
left ventricular dysfunction (LVEF < 50%)
right ventricular dysfunction (RVEF < 40%)
AND
(ii) No alternative explanation for clinical features
AND
(iii) FDG-PET uptake suggestive of active CS within two months of enrollment (confirmed by PET core lab read)
AND ONE OR BOTH OF FOLLOWING
(iv) Positive biopsy for Sarcoid (either EMB or extra-cardiac)
(v) CT Chest showing features consistent with pulmonary sarcoidosis and/or mediastinal and/or hilar lymphadenopathy
Exclusion Criteria:
Current or recent (within two months) non-topical treatment for sarcoidosis
Currently taking Methotrexate or Prednisone for another health condition
Intolerance or contra-indication to Methotrexate or Prednisone
Patient does not meet all of the above listed inclusion criteria
Patient is unable or unwilling to provide informed consent
Patient is included in another randomized clinical trial
Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
Breastfeeding
Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
Patients for whom the investigator believes that the trial is not in the interest of the patient
Prednisone or Prednisolone, Methotrexate, Prednisone or Prednisolone, Methotrexate
This is a multicenter, randomized, double-blind, placebo-controlled, study comparing the efficacy and safety of intravenous (IV) efzofitimod 3 mg/kg and 5 mg/kg versus placebo after 48 weeks of treatment.
This study will enroll adults with histologically confirmed pulmonary sarcoidosis receiving stable treatment with oral corticosteroid (OCS), with or without immunosuppressant therapy.
Maneesh Bhargava
Male or Female
18 Years and over
This study is NOT accepting healthy volunteers
STUDY00016463
STUDY00016463
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Inclusion Criteria:
Confirmed diagnosis of pulmonary sarcoidosis for at least 6 months, defined by the following criteria: documented histologically proven diagnosis of sarcoidosis by tissue biopsy and documented evidence of parenchymal lung involvement by historical radiological evidence
Evidence of symptomatic pulmonary sarcoidosis, as demonstrated by the following criteria: Modified Medical Research Council (MRC) dyspnea scale grade of at least 1 and KSQ-Lung score ≤70
Patients must be receiving treatment with OCS of ≥ 3 months with a starting dose between ≥ 7.5 and ≤ 25 mg/day.
Body weight ≥ 40 kg and < 160 kg
Exclusion Criteria:
Treatment with > 1 oral immunosuppressant therapy
Treatment with biological immunomodulators, such as tumor necrosis factor-alpha (TNF-α) inhibitors or antifibrotics or interleukin inhibitors
Likelihood of significant pulmonary fibrosis as shown by any 1 or more of the following: High resolution CT fibrosis > 20% within the last 12 months; FVC percent predicted (FVCPP) < 50% and KSQ-Lung score < 30
Clinically significant pulmonary hypertension requiring treatment with vasodilators
Patients with cardiac sarcoidosis, neurosarcoidosis, or renal sarcoidosis
Clinically significant cutaneous and ocular sarcoidosis
History of Addisonian symptoms that precluded previous OCS taper attempts
Is an active, heavy smoker of tobacco/nicotine-containing products
History of anti-synthetase syndrome or Jo-1 positive at baseline
This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglio-neuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.
Emily Greengard
All
to 30 Years old
This study is NOT accepting healthy volunteers
0807M39682
0807M39682
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Inclusion Criteria:
All newly diagnosed patients with suspected neuroblastoma, suspected ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's Oncology Group (COG) institutions are eligible for this study
There will be no penalty under any circumstances for enrollment of a patient whose definitive institutional diagnosis, or central review diagnosis, is found to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/ maturing subtype
Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and procurement of study-related tissues with the following exception:
Patients that in the opinion of the treating physician are too ill to undergo pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on ANBL00B1; documentation of the emergent nature of therapy initiation is required
It is required that a good faith effort (documented by specimen tracking) be made to submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow) of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be obtained prior to initiation of therapy
Exceptions
In rare cases, patients may be deemed too ill to undergo pre-treatment tissue biopsy and require EMERGENT therapy; the following eligibility guidelines apply to these cases:
For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g., primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT therapy initiation should be made; however, if the child is deemed too unstable for such a procedure they may still be enrolled as long as pre-treatment peripheral blood and serum have been submitted
For all other INSS stages: tumor tissue should be obtained as soon as possible within 96 hours of EMERGENT therapy initiation; patients without tumor tissues submitted within this time-frame are not eligible for enrollment
Note: it may not be possible to obtain all necessary tumor biomarkers for therapy stratification in such cases; if a patient enrolled on ANBL00B1 undergoes an additional diagnostic procedure within 96 hours of initiating therapy, additional tumor specimens may be submitted to obtain biomarkers used for risk classification; the decision to perform such procedures, and/or submit these specimens, is to be made by the managing clinicians and should reflect the clinical need to know the status of such biomarkers
Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a tumor biopsy or resection upfront; tumor tissue submission is therefore not required for these patients to enroll on ANBL00B1; a peripheral blood and serum sample is the only specimen required to be submitted for this group of patients; should they undergo a biopsy or resection at a later date tumor can be submitted for biomarker testing at this time
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1 protocol
Stratum A: Typical SCID (formerly referred to as Classic SCID)- -Subjects who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Typical SCID) of the study:
Absence or very low number of T cells (CD3 T cells <300/microliter) AND
No or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) OR
T cells of maternal origin present.
Stratum B: Leaky SCID, Omenn Syndrome, Reticular Dysgenesis-
-Subjects who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B:
Leaky SCID:
Maternal lymphocytes tested for and not detected AND
Either one or both of the following (a,b) :
a.) <50% of lower limit of normal T cell function as measured by response to PHA, OR response to anti-CD3/CD28 antibody
b.) Absent or <30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens
AND at least two of the following (a through e):
a.) Reduced number of CD3 T cells
age ≤2 years: <1500/microliter
age >2 years and ≤4 years: <800/microliter
age >4 years: <600/microliter
b.) ≥80% of CD3+ or CD4+ T cells that are CD45RO+
AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative
AND/OR >50% of CD3+ or CD4+T cells express HLA-DR (at <4 years of age)
AND/OR are oligoclonal T cells
c.) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation or compound heterozygosity with ≥1 hypomorphic mutation in an autosomal SCID-causing gene
d.) Low T Cell Receptor Excision Circles (TRECs) and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
e.) Functional testing in vitro supporting impaired, but not absent, activity of the mutant protein, AND
Does not meet criteria for Omenn Syndrome.
Omenn Syndrome:
Generalized skin rash
Maternal lymphocytes tested for and not detected;
--Note: If maternal engraftment was not assessed and ruled out, the subject is not eligible as Omenn Syndrome.
≥80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR
80% of CD3+ or CD4+T cells are CD62L negative AND/OR
50% of CD3+ or CD4+ T cells express HLA-DR (at <2 years of age);
Absent or low (< 30% lower limit of normal) T cell proliferation response to antigens (Candida, tetanus) to which the subject has been exposed
NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the subject is eligible as Omenn Syndrome:
Hepatomegaly
Splenomegaly
Lymphadenopathy
Elevated IgE
Elevated absolute eosinophil count
*Oligoclonal T cells measured by CDR3 length or flow cytometry
*Proliferation to PHA is reduced <50% of lower limit of normal or SI <30
*Hypomorphic mutation in a SCID causing gene
Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
Reticular Dysgenesis:
Absence or very low number of T cells (CD3 <300/µL
No or very low (<10% lower limit of normal) T cell response to PHA
Severe neutropenia (absolute neutrophil count < 200 /µL) AND
≥2 of the following (a,b,c):
a.) Sensori-neural deafness
b.) Deficiency of marrow granulopoiesis on bone marrow examination
c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.
Stratum C:
Subjects who meet the following criteria and the intention is to treat with therapy other than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells, are eligible for enrollment into
Stratum C:
ADA Deficient SCID with intention to treat with PEG-ADA ERT
ADA Deficient SCID with intention to treat with gene therapy
X-linked SCID with intention to treat with gene therapy
Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy)
Any SCID patient who received therapy for SCID deemed "non-standard" or "investigational", including in utero procedures.
Exclusion Criteria:
-Subjects who meet any of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study:
Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of secondary immunodeficiency
Presence of DiGeorge syndrome
MHC Class I and MHC Class II antigen deficiency, and
Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency or transcobalamin deficiency.
Severe Combined Immunodeficiency (SCID), Leaky SCID, Omenn Syndrome, Reticular Dysgenesis, ADA SCID, XSCID
Severe Combined Immunodeficiency (SCID), natural history study, SCID treatment
Treatment guidelines for high risk or relapsed solid tumors consisting of a busulfan, melphalan, thiotepa conditioning followed by an autologous peripheral blood stem cell transplant and, if appropriate, disease specific radiation therapy at day 60+
Ashish Gupta
All
to 70 Years old
N/A
This study is NOT accepting healthy volunteers
1107M02641
1107M02641
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Inclusion Criteria:
All patients must have histological verification of malignancy at original diagnosis.
Eligible Diseases
Arm A: Solid Tumor
Ewing's Family Tumors (ES/PNET/DSRCT) - metastatic at time of diagnosis and/or relapsed after therapy
Renal Tumors - relapsed (all histology - Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor)
Hepatoblastoma - metastatic at time of diagnosis and/or relapsed after therapy
Rhabdomyosarcoma - metastatic at time of diagnosis and/or relapsed after therapy
Soft Tissue Sarcoma - chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
Primary Malignant Brain Neoplasms <18 years of age - at diagnosis and/or relapse
Retinoblastoma - disseminated at diagnosis and/or relapsed
CNS Lymphoma - primary or secondary CNS lymphoma.
Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
Arm B: Certain CNS tumors
Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
> 1.5 cm2 residual disease following resection for any Medulloblastoma histology
lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
Other High Risk CNS Tumors - to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
Arm C: Germ Cell Tumors
Confirmation of germ cell tumor (GCT) histology (both seminoma and nonseminoma). Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established. This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG ≥ 500; AFP ≥ 500} and typical pattern of metastases).
One or more unfavorable prognostic features for achieving a CR with conventional-dose chemotherapy. Unfavorable prognostic features include:
extragonadal primary site
PD following an incomplete response (IR) to first-line therapy,
PD after a conventional-dose salvage (cisplatin + ifosfamide -based) regimen
Arm D: Certain CNS Tumor patients who can only undergo one transplant
Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
> 1.5 cm2 residual disease following resection for any Medulloblastoma histology
lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
Other High Risk CNS Tumors including choroid plexus carcinoma in children- to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
Arm E: Neuroblastoma ** Neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
Disease Status at Enrollment
Arm A, Arm B and Arm D must have fit one of the following:
no evidence of disease or
stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or CT and/or MRI) within 4 weeks of study entry
Arm C: Evidence of progressive or recurrent GCT (measurable or non-measurable) following one or more cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:
Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT. Patients with incomplete gross resection where viable GCT is found are considered eligible.
Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.
Arm E: Patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria.
Patients with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following:
MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
Age > 18 months (> 547 days) regardless of biologic features or
Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown.
Patients with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following:
MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or
Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.
Patients with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.
Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features.
Patients ≥ 365 days initially diagnosed with neuroblastoma INSS Stage 1, 2, 4S who progressed to aStage 4 without interval chemotherapy.
Age and Performance Status
Age and Performance Status, Arm A
Age: 0 - 70 years
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm B
Age: see Eligible diseases, section 3.1, for age criteria
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Note: Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm C
Age: 0-70 years of age
Performance status: Karnofsky Performance Status ≥ 70% for patients > 16 years of age or Lansky Play Score ≥ 70 for patients ≤ 16 years of age
Age and Performance Status, Arm D
Age: see Eligible diseases, section 3.1, for age criteria
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age (Neurologic deficits in patients with CNS tumors must be stable for a minimum of 1 week prior to study entry)
Age and Performance Status, Arm E
Age: Patients must be ≤ 30 years of age at the time of initial diagnosis.
Performance status: Karnofsky Performance Status ≥ 50% for patients > 16 years of age or Lansky Play Score ≥ 50 for patients ≤ 16 years of age
Organ Function
Organ Function, Arm A
Hematologic: hemoglobin of >9 gm/dl and platelet count > 20,000/μl. Patients may receive transfusions as necessary.
Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
Hepatic: AST or ALT ≤ 5 x ULN and bilirubin ≤ 5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 92% at rest (on room air)
Organ Function, Arm B (to begin first consolidation cycle)
Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
Renal: GFR ≥ 50 ml/min/1.73m2
Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 94% at rest (on room air)
Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
Organ Function, Arm C (to begin TI chemotherapy)
Hematologic: ANC ≥ 750/mm3, platelets ≥ 75,000/mm3
Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
Hepatic: AST or ALT ≤ 2.5 x upper limits of normal (ULN), if hepatic involvement < 5 x ULN; bilirubin ≤ 2.0 x upper limits of normal (ULN)
Arms A and C: Patients with a history of CNS tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollment
Organ Function, Arm D
Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
Hematologic: ANC > 750/μl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/μl (transfusion independent).
Renal: GFR ≥ 50 ml/min/1.73m2
Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
Pulmonary: oxygen saturation > 92% at rest (on room air)
Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
Organ Function, Arm E
No evidence of disease progression: defined as increase in tumor size of >25% or new lesions.
Timing: Recovery from last induction course of chemotherapy.
Minimum frozen PBSC of 4 x 106 CD34 cells/kg as 2 aliquots; i.e. 2 x 106 CD34 cells/kg for each transplant are mandatory. A third aliquot of 2 x 106 CD34 cells/kg is strongly recommended for back-up.
Hepatic: AST < 3 x upper normal
Cardiac: Shortening fraction ≥ 27%, or ejection fraction ≥ 50%, no clinical congestive heart failure.
Renal: Creatinine clearance or GFR > 60 ml/min/1.73m2 (If a creatinine clearance is performed at end of induction and the result is < 100 ml/min/1.73m2, a GFR must be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m2.)
Exclusion Criteria:
Arm A, B, C, and D:
Pregnant or breastfeeding
Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive constitute progressive disease.
Concomitant enrollment on clinical study (such as COG study) that does not allow co-enrollment on this standard of care protocol (Arm B only)
Arm E: Pregnant or breastfeeding
Active, uncontrolled infection and/or HIV positive
Known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (ie, non- amplified MYCN, favorable pathology, and DNA index > 1).
This therapy involves the use of consolidation chemotherapy, autologous stem cell rescue, post-transplant radiation therapy and a maintenance phase with Isotretinoin (Accutane, 13-cis-retinoic acid) therapy. If available, patients should also consider post-transplant therapy with cytokines and monoclonal antibody (ch14.18) on a COG or NANT trial. Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #6. (It is strongly recommended to begin consolidation within 4-6 weeks after starting Induction Cycle #6).
Ashish Gupta
All
to 30 Years old
N/A
This study is NOT accepting healthy volunteers
1112M07741
1112M07741
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Inclusion Criteria:
Less than 30 years of age at diagnosis of neuroblastoma
No evidence of disease progression: defined as increase in tumor size of >25% or new lesions
Recovery from last induction course of chemotherapy (absolute neutrophil count > 500 and platelet > 20,000)
No uncontrolled infection
Minimum frozen peripheral blood stem cells (PBSCs) of 2 x 10^6 CD34 cells/kg for transplant are mandatory and 2 x 10^6 CD34 cells/kg for back-up are strongly recommended (thus, PBSC of 4 x 106 CD34 cells/kg is encouraged)
Adequate organ function defined as:
Hepatic: aspartate aminotransferase (AST) < 3 x upper limit of institutional normal 8 Cardiac: shortening fraction ≥ 27% or ejection fraction ≥ 50%, no clinical congestive heart failure 8 Renal: Creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73m^2 If a creatinine clearance is performed at end induction and the result is < 100 ml/min/1.73m^2, a GFR must then be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m^2
Exclusion Criteria
Patients with progressive disease should consider participating in phase I studies since consolidation therapy using the regimen outlined in this document have not been determined to be useful.
Patients who are delayed in consolidation chemotherapy beyond 8 weeks, and don't meet organ function criteria.
This is a treatment protocol for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. There is no research element except the collection of routine clinical data.
Margaret MacMillan, MD
All
to 55 Years old
N/A
This study is NOT accepting healthy volunteers
1305M34181
1305M34181
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Inclusion Criteria:
Eligible Disease Status
Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
Very high risk pediatric patients with AML: Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
Very high risk pediatric patients with ALL: patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
Advanced Myelofibrosis
Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10% by a representative bone marrow aspirate morphology.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
Myeloproliferative Syndromes
Availability of suitable UCB unit(s)
0 to 55 years
Voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens)
if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
pregnant or breastfeeding
HIV positive
Fludarabine, Cyclophosphamide, Total Body Irradiation, Cyclosporine A, Mycophenylate mofetil, Umbilical cord blood, Fludarabine, Cyclophosphamide, Total Body Irradiation, Cyclosporine A, Mycophenylate mofetil, Umbilical cord blood
This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of busulfan, fludarabine, and low dose total body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve an acceptable level of donor-derived engraftment following a previous allogeneic HSCT. While it will primarily be applied for the treatment of non-malignant diseases (NMD), on occasion it may be used to treat patients with malignant disorders as well.
Troy Lund
All
to 55 Years old
N/A
This study is NOT accepting healthy volunteers
1207M17641
1207M17641
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Inclusion Criteria:
Diagnosis of any disease for which a second or greater hematopoietic stem cell transplant is needed due to insufficient donor chimerism following hematopoietic recovery after previous HSCT. Determination of "insufficiency of donor chimerism" will be made by the treating transplant physician. Occasionally donor derived engraftment may be present, but sustained aplasia or failed recovery of sufficient hematopoiesis requires administration of a second graft. This intervention may be used for both situations.
Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program
Transplantation using sufficiently matched related donors (such as matched siblings) or unrelated donors will be considered. Both granulocyte-colony stimulating factor (GCSF) stimulated peripheral blood grafts and bone marrow grafts will be considered, although bone marrow will be the priority.
Cord blood grafts, both related and unrelated, are also eligible. As this protocol will use a reduced intensity regimen, this protocol will use the current recommendations of the University of Minnesota for choosing cord blood grafts. If a single cord blood unit cell dose is insufficient, double cord transplantation should be considered if sufficiently matched cord blood units are available. The priority of choosing cord blood donors is based on the current institutional recommendations.
Exclusion of Metabolic Disorder or other Inherited Disorder Carrier Status from related donor and unrelated cord blood grafts as appropriate for primary disease.
At the discretion of the treating transplant physician, an allograft from the previous donor may be used, if available.
Age, Performance Status, Consent
Age: 0 to 55 years
Consent: voluntary written consent (adult or parental/guardian)
Exclusion Criteria:
Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI). Radiation Oncology will evaluate all patients who have had previous radiation therapy or TBI for approval to receive an additional 200 cGy of TBI
Pregnant or breastfeeding
Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted
HIV positive
While it would be advantageous to begin therapy on this second transplant regimen > 6 months following a prior myeloablative regimen or >2 months after a reduced intensity regimen, it is recognized that there are circumstances where this may not be practical.
Busulfan, Fludarabine, Total body irradiation, Stem cell transplant, Keppra, Busulfan, Fludarabine, Total body irradiation, Stem cell transplant, Keppra
Diagnosis of immunodeficiency or histiocytic disorder including the following:
Severe combined immunodeficiency (SCID - all variants)
Second bone marrow transplant (BMT) for SCID (after graft rejection)
Omenn's Syndrome
Reticular dysgenesis
Wiskott-Aldrich syndrome
Major histocompatibility complex (MHC) Class II deficiency (bare lymphocyte syndrome)
Hyper IgM Syndrome (CD40 Ligand Deficiency)
Common variable immunodeficiency (CVID) with severe phenotype
Chronic Granulomatous Disease (CGD)
Other severe Combined Immune Deficiencies (CID)
Hemophagocytic Lymphohistiocytosis (HLH)
X-linked Lymphoproliferative Disease (XLP)
Chediak-Higashi Syndrome (CHS)
Griscelli Syndrome
Langerhans Cell Histiocytosis (LCH)
Acceptable stem cell sources include:
HLA identical or 1 antigen matched sibling donor eligible to donate bone marrow
HLA identical or up to a 1 antigen mismatched unrelated BM donor
Sibling donor cord blood with acceptable HLA match and cell dose as per current institutional standards
Single unrelated umbilical cord blood unit with 0-2 antigen mismatch and minimum cell dose of >5 x 10^7 nucleated cells/kg as per current institutional guidelines
Double unrelated umbilical cord blood units that are:
up to 2 antigen mismatched to the patient
up to 2 antigen mismatched to each other
minimum cell dose of at least one single unit must be ≥ 3.5 x 10^7 nucleated cells/kg
combined dose of both units must provide a total cell dose of ≥ 5 x 10^7 nucleated cells/kg
Age: 0 to 50 years
Adequate organ function and performance status.
Exclusion Criteria
pregnant or breastfeeding
active, uncontrolled infection and/or HIV positive
acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Patients with primary or secondary graft failure, as defined below, may receive a second transplant:
Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant.
Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery.
Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood.
Recipients should have acceptable organ function defined as:
Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments.
Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal
Cardiac: left ventricular ejection fraction > 40%
Exclusion Criteria:
Uncontrolled infection at the time of transplant.
Patients with Fanconi Anemia or other DNA breakage syndromes.
Fludarabine, Cyclophosphamide, Total Body Irradiation, Hematopoietic stem cell infusion, Fludarabine, Cyclophosphamide, Total Body Irradiation, Hematopoietic stem cell infusion
Diagnosis of Sickle Cell Disease, Thalassemia, Diamond Blackfan Anemia or other non-malignant hematologic disorders for which a stem cell transplant is indicated
Acceptable stem cell source identified
Performance status of ≥ 70% (Karnofsky),or ≥ 70 (Lansky play score)
Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min for children
Bilirubin, Aspartate Aminotransferase, Alkaline phosphatase <5 times the upper limit of institutional normal
Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%
Exclusion Criteria:
active, uncontrolled infection
pregnant or breastfeeding
HIV positive
Aged 0 - 70 years
Acceptable hematopoeitic stem cell donor
Dyskeratosis Congenita (DC) with evidence of BM failure defined as:
requirement for red blood cell and/or platelet transfusions or
requirement for G-CSF or GM-CSF or erythropoietin or
refractory cytopenias having one of the following three
platelets <50,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
hemoglobin <9g/uL or transfusion dependent
Diagnosis of DC with a triad of mucocutaneous features:
oral leukoplakia
nail dystrophy
abnormal reticular skin hyperpigmentation, or
Diagnosis of DC with one of the following:
short telomeres (under a research study)
mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)
mutation in shelterin complex (TINF2)
mutation in telomere-capping complex (CTC1)
Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:
Refractory cytopenia defined by bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
Diagnosis of SAA with refractory cytopenias having one of the following three:
platelets <20,000/uL or transfusion dependent
absolute neutrophil count <500/uL without hematopoietic growth factor support
absolute reticulocyte count <20,000/uL
Severe Aplastic Anemia (SAA) requiring a 2nd transplant
Graft failure as defined by blood/marrow chimerism of < 5%
Early myelodysplastic features
With or without clonal cytogenetic abnormalities
Adequate organ function defined as:
cardiac: left ventricular ejection fraction ≥ 35% with no evidence of decompensated heart failure
pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement
renal: Glomerular filtration rate (GFR) ≥30% predicted
Voluntary written consent
Exclusion Criteria:
Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Pregnant or lactating
Uncontrolled infection
Prior radiation therapy (applies to SAA patients only)
Diagnosis of Fanconi anemia based on DEB
Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with >30% blasts
Alemtuzumab, Fludarabine, Cyclophosphamide, Total Body Irradiation, Stem Cell Transplant, Anti-thymocyte globulin, Alemtuzumab, Fludarabine, Cyclophosphamide, Total Body Irradiation, Stem Cell Transplant, Anti-thymocyte globulin
This protocol will characterize the effects of deep brain stimulation (DBS) location (both adverse and beneficial) on motor signs in people with Parkinson’s disease (PD). This information can be used to inform future DBS protocols to tailor stimulation to the specific needs of a patient. If targeted dorsal GP stimulation is shown to significantly improve motor features that are typically resistant to dopamine replacement therapy, these experiments will likely have major impact on clinical practice by providing a potential strategy to these medically intractable symptoms.
Colum MacKinnon
All
18 Years to 89 Years old
N/A
This study is NOT accepting healthy volunteers
1608M93561
1608M93561
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Inclusion Criteria:
diagnosis of idiopathic PD
have undergone neurosurgery to implant deep brain stimulators in the globus pallidus (GP DBS) or subthalamic nucleus (STN)
Existing 7T brain imagery
Exclusion Criteria:
history of musculoskeletal disorders that significantly affect movement of the upper or lower limbs
other significant neurological disorder
history of dementia or cognitive impairment as found with UBACC (or MacCAT-CR)
post-operative complications or adverse effects
The primary objective of the study is to assess the efficacy of patient controlled sedation (Self-management of sedative therapy) using dexmedetomidine to reduce anxiety, delirium incidence and duration of mechanical ventilation compared to usual sedation practices in mechanically ventilated subjects.
Craig Weinert
All
18 Years to old
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
1605M88241
1605M88241
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Inclusion Criteria:
Subject is acutely mechanically ventilated during the current hospitalization.
Subject is currently receiving a continuous intravenous infusion of a sedative/opioid medication(s) or has received at least one intravenous bolus dose of a sedative/opioid medication in the previous 24 hours (fentanyl, hydromorphone, ketamine, morphine, midazolam, diazepam, lorazepam, propofol, haloperidol, dexmedetomidine).
Subject must pass pre-Patient-Controlled Sedation (PCS) screening test and be assessed Richmond Agitation-Sedation Scale (RASS) -2 to +1
Subject Age ≥ 18 years
Subject or their proxy is capable of providing informed consent
Exclusion Criteria:
Aggressive ventilatory support or prone ventilation.
Hypotension (systolic blood pressure < 85 mmHg) requiring a vasopressor at a dose greater than norepinephrine or epinephrine 0.15 mcg/kg/min or vasopressin > 2.4 units per hour. Subjects will be excluded if they require more than one continuous infusion of a catecholamine vasopressor medication simultaneously. Subjects will be excluded if the vasopressor dose was higher than norepinephrine or epinephrine 0.15 mcg/kg/min, vasopressin > 2.4 units per hour, phenylephrine >3 mcg/kg/min, dopamine >10 mcg/kg/min or dobutamine at any dose in the prior 6 hours. If dopamine is being used to increase heart rate, rather than as a vasopressor for hypotension, subject will be excluded.
Second or third degree heart block or bradycardia (heart rate < 50 beats/min).
Paralysis or other condition preventing the use of push button device
Positive pregnancy test or lactation
Acute hepatitis or liver failure (direct bilirubin >5 mg/dL)
Acute stroke or uncontrolled seizures.
Acute myocardial infarction within 48 hours prior to enrollment.
Severe cognition or communication problems (such as coma, deafness without signing literacy, physician-documented dementia)
Assessed RASS -3, -4, -5 or RASS +2,+3, +4
Chronic ventilator support in place of residence prior to current hospitalization.
Imminent extubation from mechanical ventilator support.
Comorbid AUD+AnxD is a significant barrier to successful AUD treatment. Converging evidence implicates overlap in dysregulation of systems governing stress response (HPA, ANS, CNS) for symptom development in AUD and AnxD. However, this must be systematically demonstrated in comorbid AUD+AnxD.
We will assess markers of multi-system biological stress regulation (at rest and in response to laboratory challenge) in alcohol use disorder (AUD) inpatients with and without co-occurring anxiety disorder (AnxD), as well as those with AnxD who do versus do not receive a cognitive behavioral treatment that specifically targets comorbid AUD-AnxD. Laboratory measures include 1) cortisol (to assess the hypothalamic–pituitary–adrenal axis system [HPA] function; 2) heart rate variability (to assess autonomic nervous system [ANS] function), and 3) threat-potentiated startle (to assess central nervous system [CNS] function).
Laboratory assessments will occur at the following times: 1) shortly after AUD treatment admittance (Visit 2: Pre-Treatment), 2) immediately following the 4-week AUD treatment (Visit 3: Post-Treatment), 3) 1 month following AUD treatment (Visit 4: 1-Month Follow-Up), and 4) 4 months following AUD treatment (Visit 5: 4-Month Follow-Up). Self-reported alcohol intake will be assessed at baseline as well as at the 1- and 4-Month Follow-Ups to determine whether laboratory stress measures predict treatment outcomes. A single laboratory assessment of healthy controls will serve as a normative reference for characterizing patient laboratory responses in terms of dysregulation and re-regulation.
Justin Anker
All
18 Years to 65 Years old
This study is also accepting healthy volunteers
1612M02641
1612M02641
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Inclusion Criteria:
Ability to provide informed consent
Between the ages of 18 and 65
Diagnostic and Statistical Manual diagnosis of a Panic Disorder, Generalized Anxiety Disorder, or Social Anxiety Disorder within the past 30 days (AUD+AnxD group only).
Primary alcohol use disorder diagnosis and alcohol use in the 30 days preceding the study (AUD alone and AUD+AnxD groups only).
Inpatient treatment at Lodging Plus primarily for alcohol (vs. other drug with nicotine accepted) dependence (AUD alone and AUD+AnxD groups only).
A minimum of a sixth-grade reading level.
Healthy controls, same criteria absent AUD and AnxD diagnosis of an alcohol and/or anxiety disorder
Lives within proximity to the Twin Cities (e.g., within about an hour's drive) or willing to drive to Fairview for the purpose of attending follow-up visits
Willingness to provide contact information to confirm follow-up appointments
Exclusion Criteria:
Lifetime history of psychosis or mania
Cognitive impairment, physical impairment, or chronic medical illness that precludes study participation
Primary PTSD as determined by qualifying assessment
Females currently pregnant
Exposure to antipsychotic medication for a total duration >16 weeks.
Prior head injury leading to >30 minutes of unconsciousness.
Cognitive impairment that impedes study participation.
Healthy controls with a history of any major medical or psychiatric disorders (e.g., schizophrenia, depression, heart disease, or stroke).
Suicide intent or attempt in the past 30 days
Cardiovascular health issues
Thyroid Disease
History of severe neurological illness such as chronic seizure disorder (e.g, epilepsy) or stroke
Brain tumor and/or implants in the skull cavity (e.g., plate in the skull)
Pacemaker
Alcohol Use Disorder, Anxiety Disorder/Anxiety State, Stress Disorder, Hypothalamic Pituitary Adrenal, Drinking to Cope
We are doing the RARE study to learn more about Cystic Fibrosis (CF). CF is caused by mutations in a gene that produces a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). In people with CF, the CFTR does not function correctly. Medications are being developed to help the CFTR function better, but those medications mostly benefit people with common CFTR mutations.
There are more than 1,900 mutations of the CF gene. Some of these mutations are rare and found only in a few people. The goal of this research study is to collect specimens (blood, nasal cells, rectal cells) from people with rare CFTR mutations.
Another purpose of this study is to create induced pluripotent stem cells or iPS cells. “Pluripotent” stem cells are cells that can be changed into almost any cell type of the body (such as lung or intestine). They can be kept alive and stored indefinitely. There are different kinds of pluripotent stem cells. Inducted pluripotent stem cells can be created from many different kinds of specimens (such as blood, nasal cells, rectal cells). This is different from embryonic stem cells, which can only be derived from embryos.
The specimens collected during this study and iPS cells created from them will be stored for use in future research to learn more about CF and study the effect of new medications. This could identify new medications that may help people with rare CFTR mutations.
Joanne Billings
All
12 Years to old
This study is NOT accepting healthy volunteers
1702M07621
1702M07621
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Inclusion Criteria:
Male or female ≥ 12 years of age at time of consent
Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with CF and one or more of the following criteria (1. Sweat chloride ≥ 60 milliequivalents/Liter (mEq/L) by quantitative pilocarpineiontophoresis test (QPIT) OR upon permission of the RARE Investigator- Sponsors, 2. Two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene, 3.Abnormal nasal potential difference (NPD) (change in NPD in response to a low chloride solution and isoproterenol of lessthan -6.6 mV)
Confirmed genotype of the current recruitment focus for certain target rare mutations. The initial recruitment focus will be CF patients who are homozygous for pre-mature stop codons. Operations Memos will detail any future current genotype targets.
Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability to comply with the requirements of the study.
Willing to travel (if needed) to a regional study site for cell collection.
Exclusion Criteria:
Presence of a medical condition, abnormality, or laboratory value(s) that in the opinion of the onsite principal investigator and/or collaborating gastroenterologist may compromise the quality of the data or place the subject at significant risk by undergoing the research related biopsy, including:
Significantly diseased distal rectal/GI tissue that could place the participant at risk by participating in the study (as judged by the collaborating gastroenterologist, such as significant hemorrhoids, vascular abnormalities, colonic infection, radiation injury or history of radiation therapy to the rectum, prostate and/or pelvic area)
Any of the following abnormal lab values at the study visit:
i. Platelets < 50 x 10^3/µL ii. Hemoglobin < 10 gm/dL iii. Hematocrit < 30% iv. WBC > 20 x 10^3/µL v. Neutropenia (ANC < 1.5 x 10^3/µL) vi. Lymphopenia (absolute lymphocyte count < 1.5 x 10^3/µL) vii. PT/INR > 1.5 viii. Other bleeding diathesis
Positive pregnancy test (for female of childbearing potential) at the study visit.
Breastfeeding (if patient opts to use sedation).
Current use of drugs with significant risks of compromising immunity (e.g. oral steroid use >20 mg/day) for >14 days prior to the rectal biopsy.
History of organ transplant.
Use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within seven days prior to rectal biopsy.
Unable or unwilling to withhold use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such as warfarin or platelet inactivators such as aspirin) within 7 days after rectal biopsy.
The goal of this study is to provide comprehensive longitudinal assessments of a cohort of PD patients before, during, and after DBS surgery, including neurological, neurophysiological, and neuropsychological data.
Scott Cooper
All
18 Years to old
This study is NOT accepting healthy volunteers
1611M00822
1611M00822
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Inclusion Criteria:
Age 18 years and older
Diagnosis of Parkinson's disease
Candidate for DBS
Exclusion Criteria:
Other significant neurological disorder
Diagnosis of dementia
Prior history of stereotactic neurosurgery for treatment of Parkinson's disease, tremor, or dystonia.
Pregnant women
Patient's health care provider adopts and intends to apply the center's AlloSure Routine Testing Schedule as part of the information used to manage the patient.
Subjects willing to provide written informed consent to participate.
KOAR
Exclusion Criteria:
___________________________________________________________
Exclusions for AlloSure® Intended Use
Specimens from patients for whom any of the following are true will not be tested:
Recipients of transplanted organs other than kidney
Recipients of a transplant from a monozygotic (identical)
Recipients of a bone marrow transplant
Recipients who are pregnant
Recipients who are under the age of 18
Recipient who are less than 14 days post-transplant
Donor-derived cell-free DNA (AlloSure®), Standard care, Peripheral blood gene expression profiling (AlloMap Kidney), Analytic platform (IBox), Donor-derived cell-free DNA (AlloSure®), Standard care, Peripheral blood gene expression profiling (AlloMap Kidney), Analytic platform (IBox)
The purpose of this study is to better understand how switching from smoking to the use of electronic cigarettes (e-cigarettes) may change users’ exposures to various harmful chemicals. Your participation will also help us to understand how nicotine that is present in e-cigarettes is taken in and modified by your body.
Irina Stepanov
Male or Female
18 Years and over
Phase 1
This study is also accepting healthy volunteers
STUDY00002033
STUDY00002033
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Inclusion Criteria:
Male or female smokers who are 18-65 years of age and are willing to stop smoking and completely switch to e-cigarettes or medicinal nicotine;
Report smoking ≥ 5 cigarettes daily and not using any other nicotine or tobacco product;
Biochemically confirmed regular smoking status by a NicAlert test level of 6;
Smoking daily for at least 1 year and no serious quit attempts (e.g., quit for 24 hours or longer) in the last 3 months (to ensure stability of daily smoking, particularly for those randomized to the continued smoking group);
No unstable and significant medical or psychiatric conditions as determined by medical history and Prime-MD (to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures);
Subjects are in good physical health (no unstable medical condition);
Subjects are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse);
Subjects who are not taking anti-inflammatory medications or any medications that affect relevant metabolic enzymes;
Women who are not pregnant or nursing or planning to become pregnant;
Subject has provided written informed consent to participate in the study (adolescents under the age of 18 will be excluded because this project involves continued use of tobacco products and new tobacco products).
Exclusion Criteria:
Regular tobacco or nicotine product use (e.g., 9 days in last 30 days) other than cigarettes;
Currently using nicotine replacement or other tobacco cessation products;
Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data;
Unstable health conditions (any significant serious, unstable medical condition including, but not limited to, cardiovascular disease, unstable COPD, seizure disorder and cancer, as determined by the licensed medical professional);
Unstable mental health (to be determined by medical history, CESD, Prime-MD after review by the licensed medical professional);
Excessive drinking (e.g., 5 or more drinks daily) or problems with drinking or drugs (e.g., self-report of binge drinking alcohol or treatment for drug or alcohol abuse within last 3 months); to be assessed by PI or licensed medical professional;
Blood alcohol test > 0.01 (g/dL) as measured by a breath sample at screening (participants failing the breath alcohol screen will be allowed to re-screen once;
Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP. Failing temperature strip for the sample. Marijuana will be tested for, but will not be an exclusionary criterion. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded. Participants failing the toxicology screen will be allowed to re-screen once;
Pregnant or breastfeeding;
Failure to agree to take adequate protection to avoid becoming pregnant during the study;
Vital signs outside of the following range (participants failing for vital signs will be allowed to re-screen once):
Systolic BP greater than or equal to 160 mm/hg
Diastolic BP greater than or equal to 100 mm/hg
Systolic BP below 90 mm/hg and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
Diastolic BP below 50 mm/hg and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
Heart rate greater than or equal to 105 bpm
Heart rate lower than 45 bpm and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
Expired air carbon monoxide (CO) level greater than 80 ppm;
Self-reported allergies to propylene glycol or vegetable glycerin;
Adverse reactions when previously using electronic cigarettes;
Household member enrolled in the study concurrently;
Unable to read for comprehension or completion of study documents;
Unstable living environment that would compromise the ability to attend visits, sequester study products or complete study procedures outside of visits.
Standardized Research E-cigarette (SREC), Nicotine Mini-Lozenge, Standardized Research E-cigarette (SREC), Nicotine Mini-Lozenge