Incretin Action in Physiology and Diabetes

NCT ID: NCT02550548

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-21
• Study Completion Date: 2021-04-16

Brief Summary

This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies.

Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.

Conditions

Insulin Secretion

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

GIP infusion

During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages, (initial dose will be 2.0 ng/kg/min, followed by 4.0, 8.0, and 16.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes.

Group Type: EXPERIMENTAL

GIP infusion

Intervention Type: DRUG

after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused

GLP-1 infusion

During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GLP-1 infused at 4 incremental dosages, (initial dose will be 1.0 ng/kg/min, followed by 2.0, 3.0, and 4.0 ng/kg/min). Each dose will be infused continuously for 30 minutes, followed immediately by the next higher dose. The total time of this procedure is 240 minutes.

Group Type: EXPERIMENTAL

GLP-1 infusion

Intervention Type: DRUG

after establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused

GIP + GLP-1 infusion

During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP + GLP-1 infused simultaneously at 4 incremental dosages (doses will be half the amounts described above). These doses will be infused continuously for 30 minutes, followed immediately by the next higher doses. The total time of this procedure is 240 minutes.

Group Type: EXPERIMENTAL

GIP infusion

Intervention Type: DRUG

after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused

GLP-1 infusion

Intervention Type: DRUG

after establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused

GIP + Ex-9 infusion

During a 240 minute hyperglycemic clamp, subjects will have (after 90 minutes of the clamp) GIP infused at 4 incremental dosages (as described above) with Ex-9 infused at a steady dose of 2.5 mcg/kg/min starting 90 minutes before the GIP infusion and maintained throughout the clamp experiment. The total time of this procedure is 240 minutes.

Group Type: EXPERIMENTAL

GIP infusion

Intervention Type: DRUG

after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused

Ex-9 infusion

Intervention Type: DRUG

Ex-9 infusion will be initiated at start of hyperglycemic clamp (target: 125 mg/dL)

Interventions

GIP infusion

after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused

Intervention Type: DRUG

GLP-1 infusion

after establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused

Intervention Type: DRUG

Ex-9 infusion

Ex-9 infusion will be initiated at start of hyperglycemic clamp (target: 125 mg/dL)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• healthy adult volunteers
• fasting plasma glucose value ≤ 95 mg/dL, measured at screening visit
• HbA1c ≤ 5.9%, measured at screening visit

Exclusion Criteria

• history of diabetes diagnosis, including gestational diabetes
• presence of Type II diabetes mellitus among any first degree family members
• rheumatoid arthritis
• inflammatory bowel disease
• unstable angina or uncompensated heart failure
• pulmonary disorders including COPD and asthma
• malabsorptive GI disease, such as celiac disease, or gastric bypass
• significant hepatic disease
• renal insufficiency (eGFR < 60 mL/kg/min)
• anemia (hematocrit < 34%) as measured at screening visit
• pregnancy
• uncontrolled hypertension
• consumption of daily medications that alter glucose metabolism or GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

David D'Alessio, M.D.

OTHER

Sponsor Role: lead

Responsible Party

David D'Alessio, M.D.

Professor, Division Chief of Endocrinology

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Duke Center for Living

Durham, North Carolina, United States

Countries

United States

Other Identifiers

R01DK101991

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00065698

Identifier Type: -

Identifier Source: org_study_id