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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

Tracking Information
First Submitted Date  ICMJE June 30, 2020
First Posted Date  ICMJE July 7, 2020
Last Update Posted Date August 2, 2022
Actual Study Start Date  ICMJE February 1, 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion
Official Title  ICMJE A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Biological: Exendin-9,39
    Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor
  • Other: Saline
    Placebo comparator
Study Arms  ICMJE
  • Placebo Comparator: Saline
    Saline infused during the hyperglycemic clamp with escalating doses of glucagon
    Intervention: Other: Saline
  • Active Comparator: Exendin-9,39
    Exendin-9,39 infused during the hyperglycemic clamp with escalating doses of glucagon
    Intervention: Biological: Exendin-9,39
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 1, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04459338
Other Study ID Numbers  ICMJE 20-003995
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Adrian Vella, Mayo Clinic
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Adrian Vella
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Adrian Vella, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP