CP is a progressive fibro-inflammatory disease where EPI develops due to destruction of pancreatic parenchyma or pancreatic duct distortion. EPI results in maldigestion, leading to fat-soluble vitamin deficiencies, weight loss, malnutrition, and impaired quality of life (Qol). Signs and symptoms of EPI include abdominal bloating and cramping, diarrhea, foul-smelling, greasy stools (steatorrhea), and unintentional weight loss. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment of EPI. Treatment is aimed at reduction of maldigestion-related symptoms, and prevention of malnutrition and its related morbidity and mortality. CREON® is a PERT that has been FDA approved since 2009 for the treatment of EPI due to cystic fibrosis, CP, pancreatectomy, or other conditions
• Medical history of chronic pancreatitis (CP).
• Diagnosis of Exocrine Pancreatic Insufficiency (EPI).
• History of cystic fibrosis, pancreatic cancer, pancreatic surgery, gastric bypass surgery, extensive bowel surgery, inflammatory bowel disease, celiac disease, irritable bowel syndrome
This is an open-label study for patients rolling over from VX18-445-104. This study will evaluate the long-term safety and efficacy of VX-445 combination therapy in subjects with CF.
• Completed study drug treatment in parent study (VX18-445-104); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study Key
• History of study drug intolerance in parent study Other protocol defined Inclusion/Exclusion criteria may apply
This is an observational cohort study in which patients with cystic fibrosis and healthy controls will undergo one research MRI to test cognitive function and map brain structures.
• History of stroke
• History of epilepsy
• History of neurosurgical procedures
• Past or current history of severe psychiatric illness
• Pass or current history of alcohol or substance abuse
• Presence of metallic substances in body or inability to remove before imaging procedure
• History of claustrophobia or known inability to tolerate MRI
• Current pregnancy
• Inability to consent
The purpose of this research study is because Cystic Fibrosis Related Diabetes (CFRD) has been identified by the cystic fibrosis (CF) community as one of the top ten priorities for CF research. We know that high blood sugars caused by not enough insulin lead to worse lung function in CF even before diabetes develops. However, we do not know which people with abnormal blood sugars will have long term problems.
• Age >/= 6 years
• Diagnosis of cystic fibrosis
• CF patients regularly attending the CF centers
• Clinically stable in previous 3wks:
• absence of major clinical events including pulmonary exacerbations,
• no change in their habitual treatment regimen including introduction of antibiotics or steroids in the past 3 weeks
• Diagnosis of type 1 diabetes, type 2 diabetes, or MODY
• Organ transplantation
• new diagnosis of CFRD in the past 6 months
• antidiabetic treatment in past 6 mos (insulin or oral hypoglycemic agents) -patients with previous CFRD diagnosis, but not currently taking insulin/glucose-lowering medications for at least 6 months should be included
• pulmonary exacerbation associated with systemic steroid requirement in the last 6 months
• on CFTR corrector less than 6 months prior to enrollment
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.
• 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,
• 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.
• 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 103/µL ii. Hemoglobin < 10 gm/dL iii. Hematocrit < 30% iv. WBC > 20 x 103/µL v. Neutropenia (ANC < 1.5 x 103/µL) vi. Lymphopenia (absolute lymphocyte count < 1.5 x 103/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.
This is a double-blind, placebo-controlled study of the impact of daily insulin therapy on meal stimulated protein turnover in youths with cystic fibrosis and abnormal glucose tolerance.
• Diagnosis of cystic fibrosis, age 10-25 years
• A standard routine annual OGTT performed within 12 months of randomization
• Abnormal glucose tolerance, with a fasting glucose level <126 mg/dl and
• The 1-hr OGTT glucose is ≥200 mg/dl but the 2-hr glucose is <140 (INDET), OR
• The 2-hour OGTT glucose is 140-199 mg/dl (impaired glucose tolerance, IGT).
• Diagnosis of CFRD, Consensus Conference definition (45)
• Previous organ transplant, or transplant imminent during study period
• BMI percentile >95
• Treatment with systemic glucocorticoids (nasal or inhaled glucocorticoids are acceptable)
• Therapy with growth hormone or Megace
• Nighttime continuous drip gastrostomy/jejunostomy feedings
• Pregnancy or breast-feeding or plans to become pregnant during study period
• Any change in medications during the 3 months prior to the study • Exception: the new corrector/potentiator combination drug lumacaftor/ivacaftor is expected to get FDA approval in early 2015, and most CF patients with severe genotypes, including many eligible for this proposal, will receive this drug. This is not a contraindication to participation in the current proposal (and participation in other studies is not contraindicated in the PROSPECT post-marketing drug study). Though the primary effects of the combination therapy appear to be apparent after 1 month, we will wait 6 months after initiation of lumacaftor/ivacaftor before enrollment in this study to make sure subjects are in a steady state.
• Any anticipated change in medication during the 3 month study period
• Acute illness in the 6 weeks prior to enrollment
Mapping Chemical and Microbiological Heterogeneity Throughout Explanted Cystic Fibrosis Lung Specimens
We propose to study explanted tissue of patients that are scheduled to undergo single or double lung transplant surgery as a late-stage disease therapeutic strategy. The primary endpoint will be to characterize the composition of the bacterial community in the lung. The secondary endpoint will be to describe bacterial gene expression in the lower airways.
• diagnosis of cystic fibrosis
• eligible for lung transplantation
• exhausted other available therapies without success
• informed consent
• there are no exclusion criteria
CHEC-OB-17: CHaractErizing CFTR Modulated Changes in Sweat Chloride and their Association with Clinical Outcomes
Cystic fibrosis (CF) is caused by gene mutations leading to absence or dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein which functions as a chloride channel in epithelial cells lining the respiratory tract, gastrointestinal system and sweat glands. Over the past several years, CFTR modulators (small molecule therapies that improve activity of the CFTR protein) have been shown in large clinical trials to improve clinical outcomes in people with CF resulting in the FDA approval of the modulators ivacaftor and lumacaftor/ivacaftor. In clinical trials, SC measurements emerged as an important marker of CFTR activity. The CHEC-SC study is looking at SC levels in people with CF who are currently being treated with CFTR modulator therapies. This study is being done to answer the following questions: • Why do different CF patients have larger or smaller reductions in sweat chloride after treatment with CFTR modulator therapy? • Does the sweat chloride value achieved after treatment with CFTR modulator therapy impact long-term health outcomes in people with CF?
PROMISE-OB-18: A prospective study to evaluate biological and clinical effects of significantly corrected CFTR function (the PROMISE Study)
This is a prospective, multi-center observational study. The study is designed to collect specimens from and perform functional measurements on CF subjects who have been prescribed the new FDA-approved CFTR modulator Triple Combination Therapy.
BEGIN-OB-19: A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function in Infants and Young Children (BEGIN)
This is a two-part, multi-center, prospective longitudinal, exploratory study of highly effective CFTR modulators and their impact in children with CF on endocrine growth factors, the gut microbiome, respiratory microbiome, liver and pancreatic function, lung function, sweat chloride, and inflammatory markers.
SIMPLIFY-IP-19: A master protocol to test the impact of discontinuing chronic therapies in people with cystic fibrosis on highly effective CFTR modulator therapy (SIMPLIFY)
This is a master protocol with two concurrent randomized trials. It is designed to evaluate the independent effects of discontinuing hypertonic saline (Study A) and dornase alfa (Study B) in people with CF age 12 and older taking Elexacaftor/Tezacaftor/Ivacaftor (ETI) for at least 90 days prior to study screening. The primary objectives are: Study A: To determine whether discontinuing hypertonic saline is non-inferior to continuing hypertonic saline after establishment of chronic ETI, as measured by the 6-week absolute change in FEV1 % predicted Study B: To determine whether discontinuing dornase alfa is non-inferior to continuing dornase alfa after establishment of chronic ETI, as measured by the 6-week absolute change in FEV1 % predicted