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

NCT00897676 | Completed Phase 1 Results

• 2 other identifiers: 2008-10-6255R01FD004905
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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).

Conditions

Congenital Hyperinsulinism

Keywords

Hyperinsulinism; Hypoglycemia; KATP channel

Outcome Measures

Primary Outcomes (1)

• 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

  Time 0 min - time 360 min

Secondary Outcomes (5)

• Area Under the Curve (AUC) Plasma Insulin

  time 0 min to time 360 min

• Area Under the Curve (AUC) Plasma C-peptide

  time 0 min to time 360 min

• Area Under the Curve (AUC) Plasma Glucagon

  time 0 min to time 360 min

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

  time 0 to time 360 min

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

  time 0 min to time 360 min

Study Arms (2)

Vehicle first, then Exendin-(9-39)

OTHER

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); Drug: placebo

Exendin-(9-39) first then Vehicle.

OTHER

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); Drug: placebo

Interventions

Exendin-(9-39) DRUG

100-500pmol/kg/min

Exendin-(9-39) first then Vehicle.; Vehicle first, then Exendin-(9-39)

placebo DRUG

placebo (0.9% NaCl)

Also known as: (0.9% NaCl)

Exendin-(9-39) first then Vehicle.; Vehicle first, then Exendin-(9-39)

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Diva De Leon: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 35416981 DERIVED

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hyperinsulinism; Hypoglycemia

Interventions

exendin (9-39); Saline Solution

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

For safety reasons, blood glucose levels were maintained above a safety threshold (55-60mg/dL) during the study by infusing dextrose intravenously which may limit the magnitude of the effect that we will be able to detect.

Results Point of Contact

• Title: Diva DeLeon, MD
• Organization: The Children's Hospital of Philadelphia

deleon@email.chop.edu

267-426-5529

Study Officials

• Diva D DeLeon, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D. Assistant Professor of Pediatrics

Model Details: 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)

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 12, 2009
• Study Start: May 1, 2009
• Primary Completion: August 26, 2016
• Study Completion: January 1, 2017
• Last Updated: March 13, 2020
• Results First Posted: January 18, 2018

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)