Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia (FAST)

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).

Study Overview

• Status: Recruiting
• Conditions: Endogenous Hyperinsulinism
• Intervention / Treatment: Drug: Exenatide; Drug: 0.9% saline solution

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kwadwo Antwi, Dr. med.; Phone Number: + 41 61 685 85 85; Email: Kwadwo.Antwi@claraspital.ch
• Study Contact Backup: Name: Matthias Hepprich, Dr. med.; Phone Number: +41 76 277 90 54; Email: Matthias.Hepprich@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel, Division of Nuclear Medicine
    • Contact: Kwadwo Antwi, Dr. med.; Phone Number: + 41 61 685 85 85; Email: Kwadwo.Antwi@claraspital.ch
    • Principal Investigator: Kwadwo Antwi, Dr. med.
    • Sub-Investigator: Damian Wild, Prof. Dr. med.
    • Sub-Investigator: Felix Kaul, Dr. med.
    • Sub-Investigator: Tobias Heye, Dr. med.
    • Sub-Investigator: Jonathan Mudry, Dr. med
    • Sub-Investigator: Martin Freitag, PD Dr. med.
    • Sub-Investigator: Matthias Hepprich, Dr. med.
    • Sub-Investigator: Emanuel Christ, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patients with suspicion for an insulinoma fulfilling all of the following inclusion criteria are eligible for the study:

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).).

Participants as control subjects fulfilling all of the following inclusion criteria are eligible for the study:

Inclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Other Names: Day 1 Exenatide; Day 2 : 0.9% saline solution; 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.; Other Names: Day 1 : 0.9% saline solution, Day 2 Exenatide
Experimental: 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.	Drug: 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.; Other Names: Day 1 Exenatide; Day 2 : 0.9% saline solution; 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.; Other Names: Day 1 : 0.9% saline solution, Day 2 Exenatide
Experimental: 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.	Drug: 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.; Other Names: Day 1 Exenatide; Day 2 : 0.9% saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
time dependent decrease (time Δ from injection in min) of blood glucose (% or mmol/l))	time dependent decrease (time Δ from injection in min) of blood glucose (% or mmol/l)) that can best discriminate from placebo injection	within 4 hours after injection
time to symptoms	time to symptoms of the exenatide test in comparison to the placebo injection of 10ml 0.9% saline solution	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	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	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	time to symptoms in the exenatide test in comparison to the fasting test	within 4 hours after injection
change in levels of plasma glucose compared to placebo compared to placebo	change in levels of plasma glucose compared to placebo	within 4 hours after injection
change in levels of insulin compared to placebo	change in levels of insulin compared to placebo	within 4 hours after injection
change in levels of C-peptide compared to placebo	change in levels of C-peptide compared to placebo compared to placebo	within 4 hours after injection
change in levels of proinsulin compared to placebo	change in levels of proinsulin compared to placebo	within 4 hours after injection
change in levels of ß-hydroxybutyrate compared to placebo	change in levels of ß-hydroxybutyrate compared to placebo	within 4 hours after injection
costs of exenatide test setting (CHF)	Comparison of costs of exenatide test setting with fasting test setting	within 4 hours after injection

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Gottfried und Julia Bangerter-Rhyner-Stiftung
• Investigators: Study Director: Emanuel Christ, Prof. Dr. med., University Hospital of Basel, Interdisciplinary Endocrinology

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: hypoglycemia; insulin; Blood glucose; proinsulin; C-peptide; fasting test; betahydroxybutyrate
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Hypoglycemia; Hyperinsulinism; Congenital Hyperinsulinism; Nesidioblastosis; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Glucagon-Like Peptide-1 Receptor Agonists; Pharmaceutical Solutions; Exenatide
• Other Study ID Numbers: 2020-00169; qu20Antwi2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No