Cystic Fibrosis
Conditions
Keywords
CF transmembrane conductance regulator, CFTR, Gating Mutations
Brief summary
The purpose of this research study is to determine the effects of clinically prescribed ivacaftor treatment on 4-24 month old children with CF and gating mutations on sleeping energy expenditure, growth status and gut health and function.
Detailed description
Ivacaftor is a novel FDA approved therapy for patients with CF and gating mutations who are 4 months and older. This investigator-Initiated study is designed to evaluate the nutritional, growth and GI impact of ivacaftor treatment for the youngest (4-24 months) patient cohort and for whom FDA approval has recently been granted. This proposal directly extends the previous highly informative nutrition and weight gain investigation of ivacaftor treatment in the older patient cohort (1). The primary aims of the study are to evaluate the impact of 12 weeks of ivacaftor treatment in 4-24 month old subjects with CF and gating mutations on sleeping energy expenditure, growth status and gut health and function in 18 children with protocol evaluations at baseline (pre-treatment) and 6 and 12 weeks after clinically prescribed ivacaftor treatment has begun. Other outcomes of significant clinical interest in young subjects with CF will be explored. All subjects will be evaluated at the Children's Hospital of Philadelphia (CHOP) and will be recruited both regionally and nationally to ensure timely enrollment.
Interventions
DRUGIvacaftor
Ivacaftor (Kalydeco®, Vertex Pharmaceuticals Inc.) was the first of a new class of drugs that improved CFTR gating dysfunction (2, 3, 4). For such mutations (G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D) that permit CFTR expression at the cell membrane but compromise its activity.
Sponsors
Vertex Pharmaceuticals Incorporated
Children's Hospital of Philadelphia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
4 Months to 2 Years
Healthy volunteers
No
Inclusion criteria
* Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment * Age: 4-24 months of age * In their usual state of good health * A clinical decision has been made for subject to begin ivacaftor treatment * Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun.
Exclusion criteria
* On parenteral nutrition * Use of any medications which are as inhibitors or inducers of cytochrome P450 (CYP) 3A * Liver function tests elevated above 3x the reference range for age and sex * Other illness affecting growth or nutritional status * Other contraindications described for ivacaftor therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleeping Energy Expenditure | 12 Weeks | Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's SEE. Using indirect calorimetry, SEE will be assessed using a computerized metabolic cart Vmax ENCORE at each protocol visit while the child is asleep. SEE will be assessed in the morning if possible and careful note of previous feeding of the child, including the time of day, amount of food, and feeding interval prior to test |
| Anthropometric Assessment | 12 Weeks | Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's BMI. Investigators will compare the results to BMI Z scores over 12 weeks compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal Elastase I/Pancreatic Function | 12 Weeks | Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's pancreatic function. Pancreatic function will be assessed at two visits by obtaining spot stool samples with fecal elastase 1. The concentration of fecal elastase I is indicative of pancreatic function. |
| Fecal Calprotectin/Gut Inflammation | 12 Weeks | Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's gut health and function. Spot stool samples will be obtained to determine fecal calprotectin, a marker for gut inflammation. |
| Plasma Total Fatty Acids: | 4 to 6 months | Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's dietary fat absorption. A total plasma fatty acid panel will be assessed to measure the change in status of 22 fatty acids, the concentration of plasma fatty acids is indicative of dietary fat absorption. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Muscle/Fat Stores | 12 Weeks | Investigators will measure body composition to determine muscle and fat store changes over the course of 12 weeks on ivacaftor treatment compared to baseline. |
| Serum fat soluble vitamins A, D, E and K, bile acids, and serum calprotectin | 12 Weeks | Investigators will examine the changes in serum vitamin A, E, D and K concentrations after 12 weeks of Ivacaftor treatment. Additionally, investigators will examine the changes in total serum bile acids concentration and 14 bile acid species. Additionally, serum calprotectin will be obtained as a marker of lung and gut inflammation. |
| Growth Status/Growth Velocity | 12 Weeks | Investigators will observe the changes in growth status/growth velocity. This will be assessed amongst three different measurements- length (cm), weight (kg) and head circumference (cm). Each value will be used to calculate the growth velocity percentile of the subjects over the course of 12 weeks on ivacaftor treatment compared to baseline. |
| Dietary Intake | 12 Weeks | Three day weighed food record will be obtained and to determine changes in dietary caloric intake and micro and macronutrient intake over the course of 12 weeks on ivacaftor treatment. The weighed food in grams will be used to determine the calories consumed, as well as calories from fat. The caloric intake will be used to determine micro and macro nutrient intake. |
Countries
United States
Outcome results
None listed