Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Cystic Fibrosis Clinical Trial

Official title:

Role of Glucagon in Glucose Control in Cystic Fibrosis Related Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02398383
• Other study ID #: 1409014580
• Status: Completed
• Phase: Early Phase 1
• Start date: March 2015
• Est. completion date: June 22, 2017

Study information

• Verified date: June 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 22, 2017
• Est. primary completion date: June 22, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 45 Years

Eligibility

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

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis Related Diabetes
• Diabetes Mellitus
• Fibrosis

Intervention

Other:
• Oral Glucose Tolerance Test
Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Patients will drink 1.75 gm/kg glucose (Glucola) to a maximum of 75 gm. Venous samples for glucose and c-peptide will be drawn from the IV at 0, 30, 60, 90 and 120 minutes. Subjects will be instructed to eat at least 75 gm carbohydrates daily in the week prior to this test.
• Mixed Meal Tolerance Test
Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Subjects will consume 6 kcal/kg (6 ml/kg) Boost High Protein Nutritional Energy Drink (Mead-Johnson) over five minutes to a maximum of 360 ml. Venous samples for glucose, glucagon, GLP-1, GIP, and c-peptide will be drawn at -10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes.
• Hypoglycemic Clamp
All subjects with CF and adult (but not pediatric) controls will undergo one-step hypoglycemic clamp. Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling and a second IV for infusion of insulin and dextrose.

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

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