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

• ClinicalTrials.gov Identifier: NCT00897676
• Recruitment Status: Completed
• First Posted: May 12, 2009
• Results First Posted: January 18, 2018
• Last Update Posted: March 13, 2020
• Sponsor: Diva De Leon
• Information provided by (Responsible Party): Diva De Leon, Children's Hospital of Philadelphia

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Congenital Hyperinsulinism	Drug: Exendin-(9-39); Drug: placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: In a random crossover design, subjects were assigned to either intervention (6 hour infusion of exendin( 9-39) at a dose range of 100-500pmol/kg/min) or vehicle (6hr infusion of 0.9%NaCl)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
• Study Start Date: May 2009
• Actual Primary Completion Date: August 26, 2016
• Actual Study Completion Date: January 2017

Arms and Interventions

Arm	Intervention/treatment
Vehicle first, then 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.	Drug: Exendin-(9-39); 100-500pmol/kg/min; Drug: placebo; placebo (0.9% NaCl); Other Name: (0.9% NaCl)
Exendin-(9-39) first then Vehicle.; 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. .	Drug: Exendin-(9-39); 100-500pmol/kg/min; Drug: placebo; placebo (0.9% NaCl); Other Name: (0.9% NaCl)

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) Plasma Glucose [ Time Frame: 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 :

1. Area Under the Curve (AUC) Plasma Insulin [ Time Frame: 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
2. Area Under the Curve (AUC) Plasma C-peptide [ Time Frame: 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
3. Area Under the Curve (AUC) Plasma Glucagon [ Time Frame: 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
4. Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1) [ Time Frame: 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
5. Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1) [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Diva De Leon

Investigators

• Principal Investigator: Diva D DeLeon, MD; Children's Hospital of Philadelphia

More Information

• Responsible Party: Diva De Leon, M.D. Assistant Professor of Pediatrics, Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT00897676
• Other Study ID Numbers: 2008-10-6255; R01FD004905 ( Other Grant/Funding Number: US Food and Drug Administration )
• First Posted: May 12, 2009
• Results First Posted: January 18, 2018
• Last Update Posted: March 13, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Diva De Leon, Children's Hospital of Philadelphia:

Hyperinsulinism; Hypoglycemia; KATP channel

Additional relevant MeSH terms:

Congenital Hyperinsulinism; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Hypoglycemia