Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia

NCT04909333 | Completed

• 1 other identifier: 2020-00169; qu20Antwi2
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the concept of the exenatide test for diagnosis of EHH (earlier induction of symptomatic hypoglycemia compared to placebo within 4 hours after injection).

Conditions

Endogenous Hyperinsulinism

Keywords

fasting test; Blood glucose; insulin; proinsulin; C-peptide; betahydroxybutyrate; hypoglycemia

Outcome Measures

Primary Outcomes (1)

• time to symptomatic hypoglycemia after exenatide test compared to placebo

  time to symptomatic hypoglycemia after exenatide test compared to placebo

  within 4 hours after injection

Secondary Outcomes (11)

• time dependent decrease (time Δ from injection in min) of blood glucose (% or mmol/l))

  within 4 hours after injection

• time to symptoms

  within 4 hours after injection

• time to hypoglycemia (time to reach blood sugar level ≤ 2.5 mmol/l) in the exenatide test in comparison to the placebo

  within 4 hours after injection

• time to hypoglycemia (time to reach blood sugar level ≤ 2.5 mmol/l) in the exenatide test in comparison to the fasting test

  within 4 hours after injection

• time to symptoms in the exenatide test in comparison to the fasting test

  within 4 hours after injection

Study Arms (3)

Group A (EHH Patients)

EXPERIMENTAL

Group A will receive a placebo injection (0.9% saline solution) on Day 1 and 10μg Exenatide injection on Day 2.

Drug: Exenatide; Drug: 0.9% saline solution

Group B (EHH Patients)

EXPERIMENTAL

Group B will receive a 10μg Exenatide injection on Day 1 and placebo injection (0.9% saline solution) on Day 2.

Drug: Exenatide; Drug: 0.9% saline solution

Group C (control subjects)

EXPERIMENTAL

Control subjects without evidence for EHH defined by no glucose levels below 3.0 mmol/l during a 7-day CGFS (Freestyle libre) and matched to EHH patients for age, gender and BMI will receive only on one study day a single intravenous injection of 10μg Exenatide and compared to group A patients on Day 2. They will not receive a Placebo injection.

Drug: Exenatide

Interventions

Exenatide DRUG

Day1: After a standardized night meal (Maizena 40g plus dessert) at 22 p.m. on the day before, patients receive Exenatide study medication according to the randomization list (injection done slowly over 2 min.). Regular clinical examination of vegetative and neurological state will be done as well as continuous blood sugar measurements and blood withdrawals will be performed. Day2: The procedure is equal to study day 1. Instead of Exenatide, a 10ml 0.9% saline solution will be administered intravenously.

Also known as: Day 1 Exenatide; Day 2 : 0.9% saline solution

Group A (EHH Patients); Group B (EHH Patients); Group C (control subjects)

0.9% saline solution DRUG

Day1: After a standardized night meal (Maizena 40g plus dessert) at 22 p.m. on the day before, patients receive 0.9% saline solution according to the randomization list (injection done slowly over 2 min.). Regular clinical examination of vegetative and neurological state will be done as well as continuous blood sugar measurements and blood withdrawals will be performed. Day2: The procedure is equal to study day 1. Instead of 0.9% saline solution, Exenatide will be administered intravenously.

Also known as: Day 1 : 0.9% saline solution, Day 2 Exenatide

Group A (EHH Patients); Group B (EHH Patients)

Eligibility Criteria

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

You may qualify if:

• Informed Consent as documented by signature
• Biochemically proven endogenous hyperinsulinemic hypoglycemia: neuroglycopenic symptoms in the fasting state with low plasma glucose, inappropriately high serum insulin and C-peptide concentrations (standardized 72h fasting test).).
• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Possession of the adequate match criteria (age, BMI and gender) to patients with suspicion for an insulinoma

You may not qualify if:

• Known hypersensitivity or allergy to Exenatide
• Pregnant or breastfeeding female patients. A pregnancy test will be performed in all women of child bearing potential.
• Calculated creatinine clearance below 40 ml/min
• No signed informed consent
• Intake of any glucagon-like peptide (GLP)-1 analogue (such as Byetta® or Bydureon®\[= Exenatide\])
• prediabetes or diabetes (HbA1c \> 5.7 %)
• Previous abdominal surgery in the gastrointestinal tract
• Any concomitant glucose-lowering drug (i. e. insulin, sulfonyl urea)
• Any known intolerance to standardized meal (Maizena)
• Any uncontrolled significant medical, psychiatric or surgical condition (active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, uncontrolled congestive heart disease, etc.) or laboratory findings that might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study.
• Any mental conditions which prevent the patient from understanding the type, extent and possible consequences of the study and/or an uncooperative attitude from the patient

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel: collaborator

Study Sites (1)

University Hospital Basel, Division of Nuclear Medicine

Basel, 4031, Switzerland

Location

Related Publications (1)

• Hepprich M, Romberg C, Mudry J, Refardt J, Wild D, Antwi K, Christ E. Exenatide for diagnosing endogenous hyperinsulinemic hypoglycemia: a randomized placebo-controlled, double-blind, cross-over proof-of-principle study. Eur J Endocrinol. 2025 Jul 31;193(2):247-254. doi: 10.1093/ejendo/lvaf153.

  PMID: 40747712 DERIVED

MeSH Terms

Conditions

Hyperinsulinism; Insulin Resistance; Diabetes Mellitus, Insulin-Dependent, 2; Hypoglycemia

Interventions

Exenatide; Saline Solution

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Emanuel Christ, Prof. Dr. med.

  University Hospital of Basel, Interdisciplinary Endocrinology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, single-center, cross-over, placebo controlled pilot, proof of principle clinical study

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: June 1, 2021
• Study Start: April 29, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

CH (1)