Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity

Phase 1

Completed

• Conditions: Congenital Hyperinsulinism
• Interventions: Drug: Exendin-(9-39); Drug: placebo

• Registration Number: NCT00897676
• Lead Sponsor: Diva De Leon

Brief Summary

The purpose of this study is to examine the effects of exendin-(9-39) on fasting blood glucose and protein induced hypoglycemia on subjects with Congenital Hyperinsulinism. Funding Source - FDA Office of Orphan Products Development (OODP).

Detailed Description

This is a placebo controlled study with randomized crossover design to evaluate the effect of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin-(9-39), on fasting blood glucose levels, protein-induced hypoglycemia, and fasting tolerance of subjects with congenital hyperinsulinism due to mutations in the ATP- sensitive potassium channel (KATP) channel.

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-05-08
• Study First Submitted QC: 2009-05-08
• Study First Posted: 2009-05-12
• Primary Completion: 2016-08-26
• Study Completion: 2017-01
• Results First Submitted: 2017-11-09
• Results First Submitted QC: 2017-12-19
• Results First Posted: 2018-01-18
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-12
• Last Update Posted: 2020-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• Confirmed diagnosis of hyperinsulinism
• Mutation analysis results demonstrating KATP channel defect
• Age 6 months to 18 years with
• Persistent hypoglycemia

Exclusion Criteria

• Current therapy with medications that may affect glucose metabolism such as octreotide, diazoxide, high dose glucocorticoids, adrenergic agents, etc. Subjects will be eligible to participate if the last dose of octreotide is given 48 hrs before study day 1 and the last dose of diazoxide is given 72 hours before study day 1
• Evidence of a medical condition that might alter results or compromised the elimination of the peptide, including active infection, kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
• Pregnancy
• Subjects with milk protein allergy will be excluded for participating in studies involving protein tolerance test

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Vehicle first, then Exendin-(9-39)	Exendin-(9-39)	An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
Vehicle first, then Exendin-(9-39)	placebo	An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
Exendin-(9-39) first then Vehicle.	Exendin-(9-39)	An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. .
Exendin-(9-39) first then Vehicle.	placebo	An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. .

Primary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) Plasma Glucose	Time 0 min - time 360 min	Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) Plasma Insulin	time 0 min to time 360 min	Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Area Under the Curve (AUC) Plasma C-peptide	time 0 min to time 360 min	Area under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Area Under the Curve (AUC) Plasma Glucagon	time 0 min to time 360 min	Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)	time 0 to time 360 min	Area under the curve plasma total GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)	time 0 min to time 360 min	Area under the curve plasma active GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion

Trial Locations

Locations (1)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States