Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Early Phase 1

Completed

• Conditions: Cystic Fibrosis; Cystic Fibrosis Related Diabetes
• Interventions: Other: Oral Glucose Tolerance Test; Other: Mixed Meal Tolerance Test; Other: Hypoglycemic Clamp

• Registration Number: NCT02398383
• Lead Sponsor: Yale University

Brief Summary

This project is designed to begin to characterize the abnormalities of glucagon secretion in subjects with cystic fibrosis related diabetes along the spectrum of glucose tolerance. Cystic fibrosis patients with normal glucose tolerance as well as cystic fibrosis related diabetes as well as control subjects will undergo an oral glucose tolerance test, mixed meal tolerance test, and one step hypoglycemic clamp. Cystic fibrosis patients will then return 12 months later to undergo repeat mixed meal tolerance test and hypoglycemic clamp test.

Detailed Description

This project is designed to begin to characterize the abnormalities of glucagon secretion in subjects with cystic fibrosis related diabetes along the spectrum of glucose tolerance. This will be a descriptive, cross-sectional and longitudinal cohort study in a sample of children and young adults with CF and a continuum of glucose tolerance compared to healthy age-matched controls.

Cystic fibrosis patients with normal glucose tolerance as well as cystic fibrosis related diabetes as well as control subjects will be admitted to the research unit on three separate occasions to undergo an oral glucose tolerance test, mixed meal tolerance test, and one step hypoglycemic clamp. Cystic fibrosis patients will then return 12 months later to undergo repeat mixed meal tolerance test and hypoglycemic clamp test.

Study Timeline

• Study First Submitted: 2015-01-22
• Study Start: 2015-03
• Study First Submitted QC: 2015-03-19
• Study First Posted: 2015-03-25
• Primary Completion: 2017-06-22
• Study Completion: 2017-06-22
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-24
• Last Update Posted: 2020-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Diagnosis of CF by clinical or genetic determination
• Normal glucose tolerance or CFRD
• Subjects routinely taking systemic or inhaled glucocorticoids on stable regimen are eligible

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Exclusion Criteria

• Subjects with active pulmonary infection requiring supplemental doses of corticosteroids
• Use of any oral diabetes medications
• Subjects who are pregnant/lactating
• Subjects with poor compliance with pancreatic enzyme replacement therapy

Control Subjects:

Approximately 10 control subjects who are matched for age, gender, are expected to be enrolled in the study. Non-CF subjects must be >12 years old, in good health and not taking any medications or have any medical problems the doctor feels would prevent the subject from completing the study and have BMI between 15-85% for age and gender. Control subjects whose fasting blood glucose is found to be >110 mg/dL will not be continued in the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CF with Normal Glucose Tolerance	Mixed Meal Tolerance Test	Individuals with CF without cystic fibrosis related diabetes
CF with Normal Glucose Tolerance	Oral Glucose Tolerance Test	Individuals with CF without cystic fibrosis related diabetes
Cystic Fibrosis Related Diabetes	Hypoglycemic Clamp	Individuals with cystic fibrosis and cystic fibrosis related diabetes
Control	Oral Glucose Tolerance Test	Age matched control subjects
CF with Normal Glucose Tolerance	Hypoglycemic Clamp	Individuals with CF without cystic fibrosis related diabetes
Cystic Fibrosis Related Diabetes	Mixed Meal Tolerance Test	Individuals with cystic fibrosis and cystic fibrosis related diabetes
Control	Mixed Meal Tolerance Test	Age matched control subjects
Control	Hypoglycemic Clamp	Age matched control subjects
Cystic Fibrosis Related Diabetes	Oral Glucose Tolerance Test	Individuals with cystic fibrosis and cystic fibrosis related diabetes

Primary Outcome Measures

Name	Time	Method
Glucagon levels	baseline	Glucagon levels in response to to a mixed meal stimulus

Secondary Outcome Measures

Name	Time	Method
Epinephrine levels	12 months	Epinephrine and norepinephrine levels during hypoglycemic clamp
C-peptide levels	12 months	C-peptide levels during oral glucose tolerance test and mixed meal tolerance test
Hypoglycemia unawareness scores	12 months	Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey
Glucagon levels	12 months	Glucagon levels in response to to a mixed meal stimulus and difference from baseline
Norepinephrine levels	12 months	norepinephrine levels during hypoglycemic clamp
GLP-1 and GIP levels	12 months	GLP-1 and GIP levels in response to mixed meal stimulus

Trial Locations

Locations (1)

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States