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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02039986
Recruitment Status : Completed
First Posted : January 20, 2014
Last Update Posted : December 14, 2018
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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
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 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 : January 6, 2014
Actual Primary Completion Date : October 11, 2016
Actual Study Completion Date : October 11, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

all subjects
all subjects enrolled in same cohort

Primary Outcome Measures :
  1. Change from baseline in insulin secretion capacity at 16 weeks [ Time Frame: 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 :
  1. Composite change from baseline in relationships of insulin secretion and protein and interleukin levels at 16 weeks [ Time Frame: 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.

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with a confirmed diagnosis of cystic fibrosis.

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02039986

United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Principal Investigator: Andrea Kelly, MD, MSCE Children's Hospital of Philadelphia

Responsible Party: Children's Hospital of Philadelphia Identifier: NCT02039986     History of Changes
Other Study ID Numbers: 13-010465
KELLY13A0 ( Other Grant/Funding Number: Cystic Fibrosis Foundation Therapeutics, Inc. )
First Posted: January 20, 2014    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: December 2018

Keywords provided by Children's Hospital of Philadelphia:
cystic fibrosis
cystic fibrosis related diabetes

Additional relevant MeSH terms:
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action