Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia

NCT ID: NCT04909333

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-29
• Study Completion Date: 2024-04-30

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).

Detailed Description

Endogenous hyperinsulinemic hypoglycemia (EHH) is defined as inappropriate endogenous insulin secretion leading to hypoglycemia and associated symptoms. The most frequent diagnosis is an insulin-secreting pancreatic neuroendocrine tumor, but other diagnoses such as nesidioblastosis of the pancreatic islets are also possible. Biochemically, EHH is characterized by low glucose concentrations in the presence of inappropriately increased C-peptide (endogenous insulin secretion) and insulin levels. The conventional fasting test is at present the gold standard to document EHH.

Radiolabeled Exenatide for localizing insulinomas in patients with biochemically proven EHH has been evaluated and an exenatide-test in an outpatient setting may be able to replace the fasting test, by an early symptomatic hypoglycemia compared to a prolonged inpatient monitoring.

This study is to investigate the concept of the exenatide test to diagnose EHH.

Conditions

Endogenous Hyperinsulinism

Study Design

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

Study Groups

Group A (EHH Patients)

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

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: 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.

0.9% saline solution

Intervention Type: 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.

Group B (EHH Patients)

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

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: 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.

0.9% saline solution

Intervention Type: 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.

Group C (control subjects)

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.

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: 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.

Interventions

Exenatide

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.

Intervention Type: DRUG

0.9% saline solution

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.

Intervention Type: DRUG

Other Intervention Names

Day 1 Exenatide; Day 2 : 0.9% saline solution; Day 1 : 0.9% saline solution, Day 2 Exenatide

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emanuel Christ, Prof. Dr. med.

Role: STUDY_DIRECTOR

University Hospital of Basel, Interdisciplinary Endocrinology

Locations

University Hospital Basel, Division of Nuclear Medicine

Basel, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 40747712 (View on PubMed)

Other Identifiers

2020-00169; qu20Antwi2

Identifier Type: -

Identifier Source: org_study_id