Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

NCT02398383 | Completed Early Phase 1

• 1 other identifier: 1409014580
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Cystic Fibrosis Related Diabetes

Outcome Measures

Primary Outcomes (1)

• Glucagon levels

  Glucagon levels in response to to a mixed meal stimulus

  baseline

Secondary Outcomes (11)

• C-peptide levels

  baseline

• C-peptide levels

  12 months

• Epinephrine levels

  baseline

• Epinephrine levels

  12 months

• Norepinephrine levels

  baseline

Study Arms (3)

CF with Normal Glucose Tolerance

EXPERIMENTAL

Individuals with CF without cystic fibrosis related diabetes

Other: Oral Glucose Tolerance Test; Other: Mixed Meal Tolerance Test; Other: Hypoglycemic Clamp

Cystic Fibrosis Related Diabetes

EXPERIMENTAL

Individuals with cystic fibrosis and cystic fibrosis related diabetes

Other: Oral Glucose Tolerance Test; Other: Mixed Meal Tolerance Test; Other: Hypoglycemic Clamp

Control

ACTIVE COMPARATOR

Age matched control subjects

Other: Oral Glucose Tolerance Test; Other: Mixed Meal Tolerance Test; Other: Hypoglycemic Clamp

Interventions

Oral Glucose Tolerance Test OTHER

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.

CF with Normal Glucose Tolerance; Control; Cystic Fibrosis Related Diabetes

Mixed Meal Tolerance Test OTHER

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.

CF with Normal Glucose Tolerance; Control; Cystic Fibrosis Related Diabetes

Hypoglycemic Clamp OTHER

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.

CF with Normal Glucose Tolerance; Control; Cystic Fibrosis Related Diabetes

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Bracha Goldsweig, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: March 25, 2015
• Study Start: March 1, 2015
• Primary Completion: June 22, 2017
• Study Completion: June 22, 2017
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

US (1)