Effect of Physiologic Hyperglucogonemia on Adipocyte Metabolism

NCT04300049 | Completed Early Phase 1 FDA Drug

• 1 other identifier: HSC20170682H
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Purpose/Objectives: To investigate the effect of hyperglucagonemia on insulin action, particularly on adipose tissue. Research Design/Plan: Normal glucose tolerant subjects will be studied. Study subjects will receive a continuous glucagon infusion for 12 hours. Following glucagon infusion, subjects will receive prime-continuous tracer infusions for additional 4 hours to measure adipocyte metabolism. Within 6-8 weeks, subjects will return for a repeat study with normal saline as a control group. Methods: All subjects will have an oral glucose tolerance test prior to participation to confirm they are normal glucose tolerant. Subjects will be admitted to the CRC at 4 PM and will receive a continuous glucagon for 12 hours. At 6 AM on the following morning, subjects will receive prime-continuous tracer infusions of the following for 4 hours (14C-glycerol, 3-3H glucose, and D2O). At 10 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes. At 6 AM a surgical biopsy of abdominal adipose tissue will be performed for measurement of adipocyte metabolism. At 8 AM, the study team will infuse insulin/glucose to test for insulin sensitivity. Clinical Relevance: The results of this study will help the study team to further understand the pathophysiology of metabolic disturbances that is induced by hyperglucagonemia in type 2 diabetes patients.

Conditions

Insulin Sensitivity

Keywords

glucagon; Lipolysis

Outcome Measures

Primary Outcomes (1)

• the rate of glycerol turnover

  effect of glucagon infusion on whole body lipolysis,

  12 hours after the infusion

Study Arms (1)

Change in Glycerol Ra

EXPERIMENTAL

The difference in rate of lipolysis (glycerol Ra) during the basal state (-120 -0 minute) between subjects receiving glucagon and saline represents the change in whole body lipolysis caused by glucagon.

Drug: Glucagon Infusion; Other: Saline

Interventions

Glucagon Infusion DRUG

Study participants will receive glucagon infusion (6ug/kg/min for 12 hours) 12 hours.

Also known as: IV Glucagon

Change in Glycerol Ra

Saline OTHER

Study participants will receive saline infusion for 12 hours.

Also known as: Normal saline

Change in Glycerol Ra

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Fasting Glucose \< 100 mg/dl
• HbA1C \< 5.7%
• h OGTT value \< 140 mg/dl
• Good general Health as determined by medical history, physical exam, screening lab tests, urinalysis, and EKG.
• Weight Stable (±3 lbs) over the preceding 3 months
• ages from 18-50
• Male/Female
• BMI from 23-28 kg/m2 -

You may not qualify if:

• Subjects who participate in an excessively heavy exercise program.
• Subjects taking any medication known to affect glucose tolerance will be excluded.
• Cannot be pregnant
• Hyper sensitive to glucagon

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• South Texas Veterans Health Care System: collaborator

Study Sites (2)

South Texas Veterans Health Care Center

San Antonio, Texas, 78229, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Glucagon; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ralph DeFronzo, MD

  University of Texas Health San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single arm before and after glucagon vs. saline

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 9, 2020
• Study Start: February 5, 2018
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)