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Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Primary Purpose

Cystic Fibrosis, Cystic Fibrosis Related Diabetes

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Oral Glucose Tolerance Test

Mixed Meal Tolerance Test

Hypoglycemic Clamp

About this trial

This is an interventional basic science trial for Cystic Fibrosis

Eligibility Criteria

12 Years - 45 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Yale New Haven Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

CF with Normal Glucose Tolerance

Cystic Fibrosis Related Diabetes

Control

Arm Description

Individuals with CF without cystic fibrosis related diabetes

Individuals with cystic fibrosis and cystic fibrosis related diabetes

Age matched control subjects

Outcomes

Primary Outcome Measures

Glucagon levels

Glucagon levels in response to to a mixed meal stimulus

Secondary Outcome Measures

C-peptide levels

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

C-peptide levels

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

Epinephrine levels

Epinephrine and norepinephrine levels during hypoglycemic clamp

Epinephrine levels

Epinephrine and norepinephrine levels during hypoglycemic clamp

Norepinephrine levels

norepinephrine levels during hypoglycemic clamp

Norepinephrine levels

norepinephrine levels during hypoglycemic clamp

Hypoglycemia unawareness scores

Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey

Hypoglycemia unawareness scores

Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey

GLP-1 and GIP levels

GLP-1 and GIP levels in response to mixed meal stimulus

GLP-1 and GIP levels

GLP-1 and GIP levels in response to mixed meal stimulus

Glucagon levels

Glucagon levels in response to to a mixed meal stimulus and difference from baseline

Full Information

NCT ID

NCT02398383

First Posted

January 22, 2015

Last Updated

June 24, 2020

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT02398383

Brief Title

Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Official Title

Role of Glucagon in Glucose Control in Cystic Fibrosis Related Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

March 2015 (undefined)

Primary Completion Date

June 22, 2017 (Actual)

Study Completion Date

June 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis, Cystic Fibrosis Related Diabetes

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CF with Normal Glucose Tolerance

Arm Type

Experimental

Arm Description

Individuals with CF without cystic fibrosis related diabetes

Arm Title

Cystic Fibrosis Related Diabetes

Arm Type

Experimental

Arm Description

Individuals with cystic fibrosis and cystic fibrosis related diabetes

Arm Title

Control

Arm Type

Active Comparator

Arm Description

Age matched control subjects

Intervention Type

Other

Intervention Name(s)

Oral Glucose Tolerance Test

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Mixed Meal Tolerance Test

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Hypoglycemic Clamp

Intervention Description

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.

Primary Outcome Measure Information:

Title

Glucagon levels

Description

Glucagon levels in response to to a mixed meal stimulus

Time Frame

baseline

Secondary Outcome Measure Information:

Title

C-peptide levels

Description

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

Time Frame

baseline

Title

C-peptide levels

Description

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

Time Frame

12 months

Title

Epinephrine levels

Description

Epinephrine and norepinephrine levels during hypoglycemic clamp

Time Frame

baseline

Title

Epinephrine levels

Description

Epinephrine and norepinephrine levels during hypoglycemic clamp

Time Frame

12 months

Title

Norepinephrine levels

Description

norepinephrine levels during hypoglycemic clamp

Time Frame

baseline

Title

Norepinephrine levels

Description

norepinephrine levels during hypoglycemic clamp

Time Frame

12 months

Title

Hypoglycemia unawareness scores

Description

Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey

Time Frame

Baseline

Title

Hypoglycemia unawareness scores

Description

Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey

Time Frame

12 months

Title

GLP-1 and GIP levels

Description

GLP-1 and GIP levels in response to mixed meal stimulus

Time Frame

Baseline

Title

GLP-1 and GIP levels

Description

GLP-1 and GIP levels in response to mixed meal stimulus

Time Frame

12 months

Title

Glucagon levels

Description

Glucagon levels in response to to a mixed meal stimulus and difference from baseline

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bracha Goldsweig, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale New Haven Hospital

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06511

Country

United States

12. IPD Sharing Statement

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Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

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