Glucagon Dose-Response in Patients With Post-Bariatric Hypoglycemia

NCT06986603 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: STUDY00000270R01DK137518
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is to determine how blood sugar levels in individuals with and without hypoglycemia after bariatric surgery respond to different doses of glucagon, a hormone that is usually present in your body that regulates blood sugar levels. In this study, there will be 4 visits to the clinical research center. In the first visit, medical history and physical exam will be performed, and blood samples will be taken to assess overall health. During visit 2, a continuous glucose monitor will be placed under the skin. (This may be combined with visit 1, depending on the schedule of visits.) In visit 3, we will test the effect of a total of 4 different doses of glucagon, in increasing doses. In visit 4, we will test the effect of a total of 3 doses of glucagon, in decreasing doses. For both visit 3 and 4, we will infuse labeled stable glucose to allow us to measure how much glucose the body is making, and will measure levels of hormones which regulate glucose, such as insulin and glucagon.

Conditions

Hypoglycemia; Bariatric Surgery; Hypoglycemia, Reactive

Keywords

glucagon sensitivity

Outcome Measures

Primary Outcomes (2)

• Incremental change in plasma glucose levels after administration of exogenous glucagon for each dose.

  Glycemic response to exogenous glucagon for doses, as measured by incremental change in plasma glucose levels at each 30 minute step of the dose escalation protocol. AUC will be compared in each of the 2 study visits (escalation vs. deescalation).

  Measurement of glucose levels will occur at baseline, and then every 5 minutes, for 60 minutes.

• Endogenous glucose production (EGP) after administration of exogenous glucagon.

  Response to exogenous glucagon as measured by the incremental change in EGP from baseline during dose escalation or deescalation protocol.

  Measurement of glucose levels will occur at visit 2, at baseline, and then every 5 minutes after the first dose of glucagon, for 120 minutes

Secondary Outcomes (3)

• Incremental change in plasma insulin levels during glucagon dose escalation protocol

  Measurement of insulin levels will occur at baseline, and then every 30 minutes after each dosetes.

• Insulin secretion rate in response to exogenous glucagon

  Measurement of insulin secretion rates will occur at visit 2, at baseline, and then 30 minutes after each dose of glucagon

• Incremental change in GLP1 levels during glucagon dosing protocol

  Measurement will occur at visit 2, at baseline, and then every 30 minutes after each dose of glucagon

Study Arms (2)

ascending doses of glucagon

EXPERIMENTAL

Participants will receive sequential ascending doses of glucagon, 75, 150, 300, 450 micrograms during the course of the study visit.

Drug: Glucagon for Injection (Fresenius Kabi USA)

descending doses of glucagon

EXPERIMENTAL

Participants will receive sequential descending doses of glucagon - 300, 150, 75 micrograms

Drug: Glucagon for Injection (Fresenius Kabi USA)

Interventions

Glucagon for Injection (Fresenius Kabi USA) DRUG

We are assessing response to glucose, including incremental glucose values as well as changes in endogenous glucose production, insulin secretion, and glucagon levels.

ascending doses of glucagon; descending doses of glucagon

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years of age, inclusive, at screening.
• Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits.
• Males or females diagnosed with ongoing PBH, at least 2 years following Roux-en-Y gastric bypass (RYGB), with documented episodes of hypoglycemia, and history of fulfillment of Whipple's triad.

You may not qualify if:

• Documented hypoglycemia occurring only in the fasting state (\>12 hours fast);
• Current diabetes, defined as hemoglobin A1c \>6.5% or use of diabetes medications, except for acarbose or miglitol;
• Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
• Hepatic disease, including serum ALT or AST greater than 2 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin \< 3.0 g/dL; or serum bilirubin \> 2.0;
• Congestive heart failure, NYHA class II, III or IV;
• History of myocardial infarction, unstable angina or revascularization within the past 6 months.
• Two or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use.
• History of recurrent syncope (unrelated to hypoglycemia) or active diagnosis of a cardiac arrhythmia;
• Current administration of β-blocker therapy;
• History of a cerebrovascular accident;
• Seizure disorder (other than with suspect or documented hypoglycemia);
• Active treatment with long-acting (LAR) octreotide or pasireotide;
• Active malignancy, except basal cell or squamous cell skin cancers;
• Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease);
• Known insulinoma;

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• University of Alabama at Birmingham: collaborator
• University of Virginia: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

Glucagon; Injections

Condition Hierarchy (Ancestors)

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; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive either increasing doses of glucagon or decreasing doses of glucagon for visit 3, and the other during visit 4.

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 23, 2025
• Study Start: November 26, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)