Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism

NCT00571324 | Completed Phase 1 Results

• 2 other identifiers: 2007-1-5131R03DK078535-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if Exendin-(9-39), an antagonist of the glucagon-like peptide-1 (GLP-1) receptor with effects on the pancreatic beta cell, increases fasting blood glucose levels in subjects with congenital hyperinsulinism.

Conditions

Congenital Hyperinsulinism

Keywords

hyperinsulinism; hypoglycemia; KATP channel; Kir6.2

Outcome Measures

Primary Outcomes (1)

• Mean Blood Glucose Area Under the Curve (AUC 0-6h)

  To examine the effect of Exendin-(9-39) on fasting blood glucose levels, samples were collected at various time points before and during the infusion \[Exendin-(9-39) or vehicle\] including: 60 minutes before the start of the infusion, again at the start of the infusion (Time 0), and then every 20 minutes until 6 hours after the start of the infusion. Using this information, the mean blood glucose area under the curve (AUC) from the start of the infusion to the end of the infusion (360 minutes) was calculated for each both Exendin-(9-39) and vehicle and compared.

  6 hours

Secondary Outcomes (3)

• Mean Plasma Insulin Area Under the Curve (AUC 0-6h)

  6 hours

• Mean Plasma Glucagon Area Under the Curve (AUC 0-6h)

  6 hours

• Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h)

  6 hours

Study Arms (2)

Exendin-(9-39) first, the Vehicle

EXPERIMENTAL

Exendin-(9-39) will be administered intravenously (IV) after an overnight fast. Exendin-(9-39) will be infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion. The following day, after another overnight fast, normal saline (control) vehicle infusion will be administered intravenously (IV) over 6 hours. During both infusions, blood glucose levels will be measured every 20 minutes.

Drug: Exendin-(9-39); Other: Vehicle

Vehicle first, then Exendin-(9-39)

PLACEBO COMPARATOR

Normal saline vehicle infusion will be administered intravenously (IV) after an overnight fast. The infusion will be given over 6 hours. The following day, after another overnight fast, Exendin-(9-39) will be infused over 6 hours with the dose slowly escalating from 100pmol/kg/min for 2 hours, then 300pmol/kg/min for another 2 hours followed by 500pmol/kg/min for the last 2 hours of the infusion. During both infusions, blood glucose levels will be measured every 20 minutes.

Drug: Exendin-(9-39); Other: Vehicle

Interventions

Exendin-(9-39) DRUG

A short term intravenous infusion of the study drug, exendin-(9-39), will be given over 6 hours.

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

Vehicle OTHER

A short term intravenous infusion of normal saline, or the vehicle, will be given over 6 hours.

Also known as: Placebo

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

Eligibility Criteria

• Age: 7 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects with congenital hyperinsulinism

You may not qualify if:

• Acute medical illness
• History of other systemic chronic disease such as cardiac failure, renal insufficiency, hepatic insufficiency, chronic obstructive pulmonary disease, anemia, or uncontrolled hypertension
• Pregnancy
• Diabetes mellitus
• Use of medications that affect glucose metabolism, such as glucocorticoids, beta agonists, diazoxide and octreotide.
• Subjects will be eligible to participate 48 hrs after the last dose of octreotide and 72 hrs after last dose of diazoxide

Sponsors & Collaborators

• Diva De Leon: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Calabria AC, Li C, Gallagher PR, Stanley CA, De Leon DD. GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. Diabetes. 2012 Oct;61(10):2585-91. doi: 10.2337/db12-0166. Epub 2012 Aug 1.

  PMID: 22855730 DERIVED

MeSH Terms

Conditions

Congenital Hyperinsulinism; Hyperinsulinism; Hypoglycemia

Interventions

exendin (9-39)

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

Limitations and Caveats

Due to safety concerns subjects with symptomatic hypoglycemia were rescued with dextrose to maintain glucose levels \>60mg/dL limiting detectable treatment effect.

Results Point of Contact

• Title: Diva De Leon, MD
• Organization: Children's Hospital of Philadelphia

DELEON@email.chop.edu

267-426-5529

Study Officials

• Diva D De Leon, 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: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D. Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 12, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 11, 2017
• Results First Posted: November 9, 2016

Record last verified: 2017-11

Locations

US (1)