Studies of Insulin and Glucagon Action in the Liver

NCT ID: NCT07300982

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-30
• Study Completion Date: 2029-12-31

Brief Summary

This study examines how glucagon works to regulate glucose metabolism, based on new findings that suggest glucagon signaling in the liver has more than one role, and that these multiple roles can be opposing in nature. Understanding this biology provides an opportunity to develop new generations of glucagon-based drugs that target specific pathways, making them more effective at controlling blood glucose.

Participants will complete paired, 5-hour hyperinsulinemic glucose clamp visits in which they receive either glucagon or saline infusions while blood glucose is maintained and frequent blood samples are collected. The primary focus is whether coordinated glucagon and insulin signaling enhances hepatic insulin sensitivity.

Detailed Description

Volunteers will undergo screening for medical history, medication usage, and blood work; those who qualify will be offered participation. Study participation will last approximately 5-12 weeks depending on appointment availability and the number of infusions planned. This protocol involves two sets of paired procedures. Approximately 15 participants will complete each set of paired visits. Participants can opt to complete one set of paired visits or both sets of paired visits.

Set 1: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of glucagon on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a stepwise glucagon infusion will be administered.

Set 2: Each participant will complete two 5-hour hyperinsulinemic clamp procedures to examine the effects of insulin on glucose metabolism while measuring systemic glucose turnover and related blood markers. The procedures will be identical, except for the final phase of the procedure when either saline or a steady glucagon infusion will be administered.

Conditions

Diabetes (DM)

Keywords

Glucose metabolism; Hepatic insulin sensitivity; Glucagon; Insulin; hepatic glucose production

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Glucagon infusion during hyperinsulinemic clamp

Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols.

Group Type: EXPERIMENTAL

Glucagon

Intervention Type: DRUG

Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Glucagon prepared per pharmacy/bedside protocol.

Saline infusion during hyperinsulinemic clamp

Saline infusion during the final 90 minutes of an otherwise identical clamp procedure.

Group Type: PLACEBO_COMPARATOR

Saline (placebo)

Intervention Type: DRUG

IV saline infusion during clamp for 90 minutes as control.

Interventions

Glucagon

Glucagon infusion either graded (0.2→0.4→0.6 ng/kg/min) or continuous (0.4 ng/kg/min) during the final 90 minutes of a hyperinsulinemic glucose clamp. The graded or continuous glucagon infusions are given as a component of 2 separate protocols. Glucagon prepared per pharmacy/bedside protocol.

Intervention Type: DRUG

Saline (placebo)

IV saline infusion during clamp for 90 minutes as control.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy adults age 18-45 years
• Body Mass Index (BMI) < 27.0 kg/m²
• Fasting plasma glucose ≤ 95 mg/dL or HbA1c ≤ 5.8% as measured at screening visit

Exclusion Criteria

• Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
• No personal history of diabetes or pancreatitis
• No personal history of cardiac, gastrointestinal, renal or liver disease
• No history of diabetes among any first-degree family members
• Renal insufficiency (eGFR < 60 mL/kg/min)
• Anemia (hematocrit < 34%) as measured at screening visit
• Pregnant females
• Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David D'Alessio, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke Center for Living

Durham, North Carolina, United States

Countries

United States

Central Contacts

Johanna Johnson, MS

Role: CONTACT

Phone: 919-660-6766

Email: johanna.johnson@duke.edu

Alyssa Sudnick, MS

Role: CONTACT

Phone: 919-660-6769

Email: alyssa.sudnick@duke.edu

Facility Contacts

Johanna Johnson, MS

Role: primary

Alyssa Sudnick, MS

Role: backup

Other Identifiers

R01DK141090

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00117291

Identifier Type: -

Identifier Source: org_study_id