Ivacaftor Treatment in 4 Month to 2 Year Old CF Subjects

Completed

• Conditions: Cystic Fibrosis

• Registration Number: NCT03783286
• Lead Sponsor: Children's Hospital of Philadelphia

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.

Study Timeline

• Study First Submitted: 2018-12-18
• Study First Submitted QC: 2018-12-18
• Study First Posted: 2018-12-21
• Study Start: 2019-02-06
• Primary Completion: 2021-12-30
• Study Completion: 2021-12-30
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-10
• Last Update Posted: 2022-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.
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

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States