This trial is active, not recruiting.

Condition cystic fibrosis
Sponsor Children's Hospital of Philadelphia
Collaborator Vertex Pharmaceuticals Incorporated
Start date March 2014
End date February 2016
Trial size 24 participants
Trial identifier NCT02141464, 13-010622


Ivacaftor is a novel, FDA approved new therapy that addresses Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunctions in subjects with Cystic fibrosis (CF) and "gating mutations".

The primary aim is to determine the mechanism(s) for weight gain in participants whom Ivacaftor treatment was initiated based on clinical indications by CF Care Team. This longitudinal study will assess in detail energy expenditure, weight gain, body composition, and lung function in 24 subjects ≥6 years old with CF with a gating mutation before treatment and after three months treatment with Ivacaftor. All subjects will be seen at the Children's Hospital of Philadelphia's Clinical Translational Research Center.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective

Primary Outcomes

Reduction in resting energy expenditure
time frame: 3 months

Eligibility Criteria

All participants at least 6 years old.

Inclusion Criteria: - Cystic fibrosis with one or two CFTR gating mutations - Age: 6 years and older - A clinical decision has been made for the subject to start Ivacaftor treatment - In usual state of good health - Family and subject commitment to the 3-month study protocol with two, 3-4 day visits to CHOP Exclusion Criteria: - FEV1 < 40% predicted - Use of any inhibitors or inducers of cytochrome P450 (CYP) 3A - Pregnancy or breast feeding - Other illness affecting growth or nutritional status - Subjects receiving total parenteral nutrition

Additional Information

Official title Energy Balance and Weight Gain With Ivacaftor Treatment of CFTR Gating Mutations
Principal investigator Virginia Stallings, MD
Description Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a chloride channel. Most CF mutations either reduce the number of CFTR channels at the cell surface (synthesis or processing mutations) or impair channel function (gating or conductance mutations). Ivacaftor (Kalydeco, VX-770) is a novel, FDA approved new therapy that addresses CFTR dysfunctions in subjects with CF and "gating mutations", specifically; it potentiates CFTR channel function. For mutations like G551D that permit CFTR expression at the cell membrane but compromise its activity, Ivacaftor increases the probability that the channel is open and active. In previous randomized, double-blind, placebo controlled trials, Ivacaftor treatment resulted in clinically significantly improvements in pulmonary function, weight and body mass index (BMI), and significant decreases in sweat chloride reflective of increased CFTR activity. The improvements in lung function and weight occurred over the first 8 weeks of treatment, plateaued and were sustained over the 48 weeks of the trial. The mechanism for the rapid and sustained weight gain is not known. Several mechanisms are considered in this proposal which may result in improved energy balance and energy utilization, and weight gain. These include decreased resting energy expenditure, increased energy and fat absorption from the gut, improved pancreatic enzyme and pH secretion, and increased energy intake. Improvements in weight and BMI status are expected to result from this improvement in energy balance and utilization, with potential beneficial effects on muscle mass and function and quality of life.
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Children's Hospital of Philadelphia.