Energy Balance and Weight Gain With Ivacaftor Treatment
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Obesity Weight Loss, Pulmonary |
| Therapuetic Areas: | Endocrinology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 6 - Any |
| Updated: | 2/18/2017 |
| Start Date: | March 2014 |
| End Date: | June 2017 |
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.
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.
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.
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.
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
We found this trial at
1
site
South 34th Street
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
215-590-1000
Principal Investigator: Virginia Stallings, MD
Phone: 267-426-9381
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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