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Completed

NCT Number: NCT00571324

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

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.

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Key information

Conditions

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

Age range

7 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

About this study

This is an open-label, pilot study , to determine if Exendin-(9-39), an antagonist of the glucagon-like peptide-1 (GLP-1) receptor with effects on the pancreatic beta cells, increases fasting blood glucose levels in subjects with congenital hyperinsulinism. Our overall hypothesis is that abnormal GLP-1 secretion resulting from dysfunctional nutrient sensing in intestinal L-cells plays a role in the dysregulated insulin secretion characteristic of this disorder, and that antagonism of the GLP-1 receptor will increase fasting blood glucose levels.

Aim 1. To evaluate the dose of exendin-(9-39) required to elevate fasting blood glucose levels in subjects with congenital hyperinsulinism due to KATP channel mutations.

Aim 2. To determine therapeutic plasma levels, plasma half-life and pharmacokinetics of exendin-(9-39) during an intravenous short-term infusion in subjects with congenital hyperinsulinism due to Adenosine triphosphate (ATP)-sensitive potassium channel (KATP) mutations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects with congenital hyperinsulinism

Exclusion criteria

  • 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

Treatment and study plan

Exendin-(9-39)

Drug

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

Vehicle

Other

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

Other names: Placebo

Primary outcomes

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

    Time frame: 6 hours

    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.

Secondary outcomes

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

    Time frame: 6 hours

    To examine the effect of Exendin-(9-39) on plasma insulin 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 plasma insulin 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.

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

    Time frame: 6 hours

    To examine the effect of Exendin-(9-39) on plasma glucagon 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 plasma glucagon 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.

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

    Time frame: 6 hours

    To examine the effect of Exendin-(9-39) on plasma intact glucagon-like Peptide-1 (GLP-1) 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 intact GLP-1 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.

Sponsors and collaborators

Lead sponsor

Diva De Leon

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • National Institutes of Health (NIH)

Registry information

Official study title

An Open Label Pilot Study of the Effects of the Glucagon-like Peptide-1 Receptor Antagonist, Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism

Important dates

Study start
2007
Primary completion
2014
Study completion
2014
First posted
Dec 12, 2007
Registry last updated
Dec 11, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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