Endogenous Hyperinsulinism
Conditions
Keywords
fasting test, Blood glucose, insulin, proinsulin, C-peptide, betahydroxybutyrate, hypoglycemia
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.
Interventions
DRUGExenatide
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.
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.
Sponsors
Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Prospective, single-center, cross-over, placebo controlled pilot, proof of principle clinical study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| time to symptomatic hypoglycemia after exenatide test compared to placebo | within 4 hours after injection | time to symptomatic hypoglycemia after exenatide test compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in levels of C-peptide compared to placebo | within 4 hours after injection | change in levels of C-peptide compared to placebo compared to placebo |
| change in levels of proinsulin compared to placebo | within 4 hours after injection | change in levels of proinsulin compared to placebo |
| change in levels of ß-hydroxybutyrate compared to placebo | within 4 hours after injection | change in levels of ß-hydroxybutyrate compared to placebo |
| 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 symptoms | within 4 hours after injection | time to symptoms of the exenatide test in comparison to the placebo injection of 10ml 0.9% saline solution |
| 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 test | 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 symptoms 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 |
| change in levels of plasma glucose compared to placebo compared to placebo | within 4 hours after injection | change in levels of plasma glucose compared to placebo |
| change in levels of insulin compared to placebo | within 4 hours after injection | change in levels of insulin compared to 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 placebo |
Countries
Switzerland
Outcome results
None listed