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

Primary Purpose

Congenital Hyperinsulinism

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Exendin-(9-39)

placebo

About this trial

This is an interventional treatment trial for Congenital Hyperinsulinism focused on measuring Hyperinsulinism, Hypoglycemia, KATP channel

Eligibility Criteria

6 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Vehicle first, then Exendin-(9-39)

Exendin-(9-39) first then Vehicle.

Arm Description

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.

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. .

Outcomes

Primary Outcome Measures

Area Under the Curve (AUC) Plasma Glucose

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

Area Under the Curve (AUC) Plasma Insulin

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

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

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)

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)

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

Full Information

NCT ID

NCT00897676

First Posted

May 8, 2009

Last Updated

March 12, 2020

Sponsor

Diva De Leon

1. Study Identification

Unique Protocol Identification Number

NCT00897676

Brief Title

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

Official Title

Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

August 26, 2016 (Actual)

Study Completion Date

January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Diva De Leon

4. Oversight

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Hyperinsulinism

Keywords

Hyperinsulinism, Hypoglycemia, KATP channel

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

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)

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vehicle first, then Exendin-(9-39)

Arm Type

Other

Arm Description

Arm Title

Exendin-(9-39) first then Vehicle.

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Exendin-(9-39)

Intervention Description

100-500pmol/kg/min

Intervention Type

Drug

Intervention Name(s)

placebo

Other Intervention Name(s)

(0.9% NaCl)

Intervention Description

placebo (0.9% NaCl)

Primary Outcome Measure Information:

Title

Area Under the Curve (AUC) Plasma Glucose

Description

Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion

Time Frame

Time 0 min - time 360 min

Secondary Outcome Measure Information:

Title

Area Under the Curve (AUC) Plasma Insulin

Description

Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion

Time Frame

time 0 min to time 360 min

Title

Area Under the Curve (AUC) Plasma C-peptide

Description

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

Time Frame

time 0 min to time 360 min

Title

Area Under the Curve (AUC) Plasma Glucagon

Description

Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion

Time Frame

time 0 min to time 360 min

Title

Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)

Description

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

Time Frame

time 0 to time 360 min

Title

Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)

Description

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

Time Frame

time 0 min to time 360 min

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Diva D DeLeon, MD

Organizational Affiliation

Children's Hospital of Philadelphia

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35416981

Citation

Stefanovski D, Vajravelu ME, Givler S, De Leon DD. Exendin-(9-39) Effects on Glucose and Insulin in Children With Congenital Hyperinsulinism During Fasting and During a Meal and a Protein Challenge. Diabetes Care. 2022 Jun 2;45(6):1381-1390. doi: 10.2337/dc21-2009.

Results Reference

derived

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

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