Clinical trial NCT02039986: Ivacaftor (Kalydeco) and Insulin in Cystic Fibrosis (CF)
Official title: Effects of Ivacaftor (Kalydeco) Treatment Upon Insulin and Incretin Secretion in Patients With Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis Related Diabetes
Cystic Fibrosis
Keywords: cystic fibrosis
CF
cystic fibrosis related diabetes
CFRD
kalydeco
ivacaftor
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2014-01-20
Enrollment: 13
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a confirmed diagnosis of cystic fibrosis.

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change from baseline in insulin secretion capacity at 16 weeks
timeFrame: baseline and 16 weeks
Secondary outcomes:
measure: Composite change from baseline in relationships of insulin secretion and protein and interleukin levels at 16 weeks
timeFrame: baseline and 16 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Andrea Kelly, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: