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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04459338
Recruitment Status : Active, not recruiting
First Posted : July 7, 2020
Last Update Posted : August 2, 2022
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Adrian Vella, Mayo Clinic

Study Description
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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.

Condition or disease Intervention/treatment Phase
Healthy Biological: Exendin-9,39 Other: Saline Phase 3

Detailed Description:
Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Glucagon

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Saline
Saline infused during the hyperglycemic clamp with escalating doses of glucagon
 Other: Saline
Placebo comparator
Active Comparator: Exendin-9,39
Exendin-9,39 infused during the hyperglycemic clamp with escalating doses of glucagon
 Biological: Exendin-9,39
Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor


Outcome Measures
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Primary Outcome Measures :
  1. Beta-cell responsivity (Φ) [ Time Frame: It will be quantified hourly during the course of the experiment (0-300 minutes) ]
    This is an index of insulin secretion calculated using the minimal modelfor the prevailing glucose concentration.


Eligibility Criteria
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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 20 weight-stable, non-diabetic subjects

Exclusion Criteria:

  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04459338


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Adrian Vella
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Adrian Vella, MD Mayo Clinic
More Information
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Additional Information:

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Responsible Party: Adrian Vella, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT04459338    
Other Study ID Numbers: 20-003995
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No