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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Cystic Fibrosis Related Diabetes

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 Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The 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

Patients with a confirmed diagnosis of cystic fibrosis.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
all subjects; all subjects enrolled in same cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in insulin secretion capacity at 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.	baseline and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite change from baseline in relationships of insulin secretion and protein and interleukin levels at 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.	baseline and 16 weeks

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Andrea Kelly, MD, MSCE, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2014
• Primary Completion (Actual): October 11, 2016
• Study Completion (Actual): October 11, 2016

Study Registration Dates

• First Submitted: January 16, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimate): January 20, 2014

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: cystic fibrosis; CF; cystic fibrosis related diabetes; CFRD; ivacaftor; kalydeco
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 13-010465; KELLY13A0 (Other Grant/Funding Number: Cystic Fibrosis Foundation Therapeutics, Inc.)