Energy Balance and Weight Gain With Ivacaftor Treatment

Energy Balance and Weight Gain With Ivacaftor Treatment of CFTR Gating Mutations

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

24 subjects ≥6 years old with CF with a gating mutation before treatment (baseline) and after three months treatment with Ivacaftor.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in resting energy expenditure	3 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Stallings VA, Sainath N, Oberle M, Bertolaso C, Schall JI. Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations. J Pediatr. 2018 Oct;201:229-237.e4. doi: 10.1016/j.jpeds.2018.05.018. Epub 2018 Jul 18.
• Sainath NN, Schall J, Bertolaso C, McAnlis C, Stallings VA. Italian and North American dietary intake after ivacaftor treatment for Cystic Fibrosis Gating Mutations. J Cyst Fibros. 2019 Jan;18(1):135-143. doi: 10.1016/j.jcf.2018.06.004. Epub 2018 Jul 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: May 15, 2014
• First Submitted That Met QC Criteria: May 16, 2014
• First Posted (Estimate): May 19, 2014

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Body Weight; Genetic Diseases, Inborn; Body Weight Changes; Pancreatic Diseases; Cystic Fibrosis; Weight Gain
• Other Study ID Numbers: 13-010622