Clinical trial NCT01852448: Genetics of Insulin and Incretins in Cystic Fibrosis
Official title: Evaluation of the Enteroinsular Axis in Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
First posted: 2013-05-13
Enrollment: 550
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Cystic Fibrosis age \>2 yrs

Brief summary: Cystic fibrosis related diabetes (CFRD) is associated with worse CF-relevant outcomes.

The mechanisms underlying CFRD development are not fully understood, but recent evidence suggests Type 2 Diabetes Mellitus (T2DM) mechanisms may be involved and may involve incretins (gut secreted hormones that augment insulin secretion in response to a nutrient load).

This study will examine the prevalence of Genome wide association study (GWAS)-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in CF and will use this information to compare incretin and insulin secretion in non-diabetic children and adults with high risk and low risk alleles.

Detailed description: CFRD is associated with worse nutritional status, greater pulmonary function decline, and increased mortality, highlighting its relevance in CF and 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. Genome-wide association studies have associated genetic variants in TCF7L2, a transcription factor implicated in enteroendocrine function, with increased susceptibility to T2DM and CFRD.

The Objectives of this study are to perform targeted sequencing of TCF7L2 and other GWAS-associated T2DM genes in the pediatric and adult CF populations and then to compare insulin secretory capacity, β-cell sensitivity to glucose, and incretin secretion in non-diabetic CF subjects with high and low-risk alleles.

Phase 1 will include 450-500 subjects (Children age\>= 2 years, adolescents, and adults) for TCF7L2 genotype and ten other GWAS-implicated T2DM genes. The distribution of TCF7L2 and other GWAS-implicated T2 DM genes across the spectrum of glucose abnormalities will be described. Phase 1 requires a single blood or saliva sample and review of medical records.

Eligibility criteria: Inclusion Criteria

1. Subjects age \>2y
2. Diagnosis of Cystic Fibrosis
3. For subjects\< 18 years, parental/guardian permission (informed consent) and if appropriate, child assent

Exclusion Criteria 1. Established diagnosis of non-CFRD (cystic fibrosis related diabetes) (e.g T1DM)

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Primary outcomes:
measure: Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes.
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hopsital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: The University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Andrea Kelly, MD
role: PRINCIPAL_INVESTIGATOR
References: