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Exenatide-test for Diagnosing Endogenous Hyperinsulinemic Hypoglycemia

Not Applicable
Completed
Conditions
Endogenous Hyperinsulinism
Interventions
Drug: 0.9% saline solution
Registration Number
NCT04909333
Lead Sponsor
University Hospital, Basel, Switzerland
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Group A (EHH Patients)0.9% saline solutionGroup A will receive a placebo injection (0.9% saline solution) on Day 1 and 10μg Exenatide injection on Day 2.
Group B (EHH Patients)0.9% saline solutionGroup B will receive a 10μg Exenatide injection on Day 1 and placebo injection (0.9% saline solution) on Day 2.
Group A (EHH Patients)ExenatideGroup A will receive a placebo injection (0.9% saline solution) on Day 1 and 10μg Exenatide injection on Day 2.
Group C (control subjects)ExenatideControl 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 B (EHH Patients)ExenatideGroup B will receive a 10μg Exenatide injection on Day 1 and placebo injection (0.9% saline solution) on Day 2.
Primary Outcome Measures
NameTimeMethod
time to symptomatic hypoglycemia after exenatide test compared to placebowithin 4 hours after injection

time to symptomatic hypoglycemia after exenatide test compared to placebo

Secondary Outcome Measures
NameTimeMethod
time to symptomswithin 4 hours after injection

time to symptoms of the exenatide test in comparison to the placebo injection of 10ml 0.9% saline solution

time dependent decrease (time Δ from injection in min) of blood glucose (% or mmol/l))within 4 hours after injection

time dependent decrease (time Δ from injection in min) of blood glucose (% or mmol/l)) that can best discriminate from placebo injection

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

change in levels of plasma glucose compared to placebo compared to placebowithin 4 hours after injection

change in levels of plasma glucose compared to placebo

time to symptoms in the exenatide test in comparison to the fasting testwithin 4 hours after injection

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

change in levels of proinsulin compared to placebowithin 4 hours after injection

change in levels of proinsulin compared to placebo

change in levels of ß-hydroxybutyrate compared to placebowithin 4 hours after injection

change in levels of ß-hydroxybutyrate compared to placebo

costs of exenatide test setting (CHF)within 4 hours after injection

Comparison of costs of exenatide test setting with fasting test setting

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

change in levels of insulin compared to placebowithin 4 hours after injection

change in levels of insulin compared to placebo

change in levels of C-peptide compared to placebowithin 4 hours after injection

change in levels of C-peptide compared to placebo compared to placebo

Trial Locations

Locations (1)

University Hospital Basel, Division of Nuclear Medicine

🇨🇭

Basel, Switzerland

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