Ivacaftor (Kalydeco) and Insulin in Cystic Fibrosis (CF)

Sponsor

Children's Hospital of Philadelphia (Other)

Overall Status

Completed

CT.gov ID

NCT02039986

Collaborator

(none)

Enrollment

Location

33.1

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is aimed at better understanding the impact of ivacaftor upon insulin and incretin secretion and glucose tolerance in patients with Cystic Fibrosis with a glycine (G551D) mutation. Investigators hypothesize that treatment with ivacaftor improves insulin secretion in individuals with CF.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Related Diabetes Cystic Fibrosis

Detailed Description

Cystic Fibrosis Related Diabetes (CFRD) is associated with worse nutritional status, greater pulmonary function decline, and increased mortality, highlighting its relevance in Cystic Fibrosis (CF). CFRD arises primarily from compromised insulin secretion - traditionally considered a by-product of pancreatic exocrine tissue damage and fibrosis. Recent developments in the field of diabetes are propelling a re-examination of this basic explanation. The impact of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor, upon insulin secretion and glucose regulation has not been examined, but improved glucose tolerance has been appreciated anecdotally. This study aims to understand the impact of ivacaftor therapy upon blood glucose and insulin and incretin secretion.

Study Design

Study Type:

Observational

Actual Enrollment :

13 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Effects of Ivacaftor (Kalydeco) Treatment Upon Insulin and Incretin Secretion in Patients With Cystic Fibrosis

Actual Study Start Date :

Jan 6, 2014

Actual Primary Completion Date :

Oct 11, 2016

Actual Study Completion Date :

Oct 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
all subjects all subjects enrolled in same cohort

Outcome Measures

Primary Outcome Measures

Change from baseline in insulin secretion capacity at 16 weeks [baseline and 16 weeks]
To compare insulin secretion and maximal insulin secretory capacity prior to initiation of ivacaftor and after 16 weeks of ivacaftor treatment in subjects with CF and at least one G551D CFTR mutation, or other CFTR gating mutation, and to explore the impact of ivacaftor upon incretin secretion, incretin regulation of insulin secretion, and glucose excursion during a mixed meal tolerance test in CF.

Secondary Outcome Measures

Composite change from baseline in relationships of insulin secretion and protein and interleukin levels at 16 weeks [baseline and 16 weeks]
To explore the composite relationships of insulin secretion, maximal insulin secretory capacity, and incretin secretion with secreted frizzled protein-4 levels and interleukin 1β levels.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

6 yrs or older with cystic fibrosis
at least one G551D CFTR mutation or other non-G551D gating mutation, or residual function CFTR mutation such as, but not limited to, R117H mutation, for which ivacaftor is to be initiated.
Plan to initiate ivacaftor treatment for FDA approved indications by clinical care team or as part of an ongoing study of ivacaftor for other CFTR mutations, including gating mutations, or residual function mutations.
not pregnant

Exclusion Criteria:

established diagnosis of non-CF related diabetes (ie., Type I diabetes)
history of clinically symptomatic pancreatitis in past year
prior lung or liver transplant
severe CF liver disease
fundoplication-related dumping syndrome
medical co-morbidities that are not CF-related or are unstable per the Investigator opinion
acute CF pulmonary exacerbation within 4 weeks prior to study procedures
treatment with oral or intravenous corticosteroids within 4 weeks of study
hemoglobin <10g/dL within 90 days of GPA test or at Screening
abnormal renal function within 90 days of GPA test or at Screening
long-standing CFRD with fasting hyperglycemia, elevated HbA1C (>8) beyond time surrounding diagnosis of CFRD, significant basal insulin requirement
inability to perform study specific procedures (MMTT, GPA).