A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion

NCT04459338 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 20-0039955R01DK126206-03
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion

  This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).

  Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study

Study Arms (2)

Saline, Then Exendin-9,39

EXPERIMENTAL

A week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.

Biological: Exendin-9,39; Other: Saline

Exendin-9,39, Then Saline

EXPERIMENTAL

A week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.

Biological: Exendin-9,39; Other: Saline

Interventions

Exendin-9,39 BIOLOGICAL

Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor

Exendin-9,39, Then Saline; Saline, Then Exendin-9,39

Saline OTHER

Placebo comparator

Exendin-9,39, Then Saline; Saline, Then Exendin-9,39

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• weight-stable, non-diabetic subjects

You may not qualify if:

• Age \< 25 or \> 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
• HbA1c ≥5.9%
• Use of glucose-lowering agents.
• For female subjects: positive pregnancy test at the time of enrollment or study
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.

Sponsors & Collaborators

• Adrian Vella: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Adrian Vella
• Organization: Mayo Clinic

vella.adrian@mayo.edu

507-284-3754

Study Officials

• Adrian Vella, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 7, 2020
• Study Start: March 4, 2021
• Primary Completion: June 14, 2022
• Study Completion: June 14, 2022
• Last Updated: June 9, 2023
• Results First Posted: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)