Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Genetics of Insulin and Incretins in Cystic Fibrosis

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.
 
ClinicalTrials.gov Identifier: NCT01852448
Recruitment Status : Active, not recruiting
First Posted : May 13, 2013
Last Update Posted : April 24, 2020
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Tracking Information
First Submitted Date May 9, 2013
First Posted Date May 13, 2013
Last Update Posted Date April 24, 2020
Study Start Date May 2013
Estimated Primary Completion Date July 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 9, 2013)
Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes. [ Time Frame: 1 day ]
To examine the prevalence of GWAS-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in children and adults with CF.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: May 9, 2013)
Glucose-Potentiated Arginine Stimulation Test (GPA test) [ Time Frame: 1 day ]
Pancreatic ß-cell function will be evaluated using the GPA test which can be used to measure β-cell secretory capacity and sensitivity to glucose.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 9, 2013)
Mixed Meal Tolerance Testing (MMTT) [ Time Frame: 1 day ]
Incretin and insulin secretion as well as glucose tolerance will be assessed using the MMTT.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Genetics of Insulin and Incretins in Cystic Fibrosis
Official Title Evaluation of the Enteroinsular Axis in Cystic Fibrosis
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 350 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 sample and review of medical records.

Phase 2 will include a subset of 30 non-diabetic children (age >8) and adults who will have insulin and incretin secretion studies performed to look at how the body secretes insulin and other hormones in relation to having or not having these "diabetes" genes. These studies include Glucose Potentiated Arginine Tests (GPA, which measures β-cell secretory capacity and sensitivity to glucose) and Mixed Meal Tolerance Test (MMTT, which measures incretin and insulin secretion).

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population Patients with Cystic Fibrosis age >2 yrs
Condition Cystic Fibrosis
Intervention
  • Genetic: Blood or Saliva Sample Collection
    A blood or saliva sample will be obtained for genotyping of TCF7L2 and approximately ten other genes implicated in type 2 diabetes.
  • Other: Glucose -potentiated arginine (GPA) stimulation tests
    Glucose -potentiated arginine (GPA) stimulation tests and mixed meal tolerance tests (MMTT) will be performed on two separate days in the outpatient setting.
Study Groups/Cohorts Patients with Cystic Fibrosis
Blood or Saliva Sample Collection and Glucose -potentiated arginine (GPA) stimulation tests will be completed for all enrolled patients.
Interventions:
  • Genetic: Blood or Saliva Sample Collection
  • Other: Glucose -potentiated arginine (GPA) stimulation tests
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Estimated Enrollment
 (submitted: May 9, 2013)
350
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 2025
Estimated Primary Completion Date July 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria

FIRST PHASE OF STUDY:

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)

.

SECOND PHASE OF STUDY:

Inclusion Criteria

  1. Subjects age >8y
  2. Diagnosis of Cystic Fibrosis
  3. pancreatic insufficient
  4. negative urine pregnancy test at enrollment
  5. TCF7L2 rs7903146 genotype of T/T or C/C
  6. For subjects< 18 years, parental/guardian permission (informed consent) from both parents and if appropriate, child assent

Exclusion Criteria

  1. Established diagnosis of non-CF diabetes (i.e. T1DM) or CFRD
  2. History of clinically symptomatic pancreatitis within last year
  3. Prior lung or liver transplant
  4. Severe CF liver disease, as defined by presence of portal hypertension
  5. Fundoplication-related dumping syndrome
  6. Medical co-morbidities that are not CF-related or are unstable per the Investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
  7. Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
  8. Treatment with oral or intravenous corticosteroids within 6 weeks of study
  9. Hemoglobin <10 g/dL, within 90 days of Day 1 or at Screening
  10. Abnormal renal function, within 90 days of Day 1 or at Screening; defined as creatinine >2x upper limit of normal (ULN) or potassium > 5.5 milliequivalent per liter {mEq/L} on non-hemolyzed specimen
  11. Weight< 26 kg (limit for blood draw is 5 mL/kg/day; GPA requires 130 mL)
  12. Inability to perform study specific procedures (MMTT, GPA)
  13. Parents/guardians or subjects who, in study team opinion, may be non-compliant with study procedure
  14. Pregnant or lactating females.
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01852448
Other Study ID Numbers 12-009589
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Children's Hospital of Philadelphia
Study Sponsor Children's Hospital of Philadelphia
Collaborators University of Pennsylvania
Investigators
Principal Investigator: Andrea Kelly, MD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date April 2020