Clinical trial NCT00571324: Effect of Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Congenital Hyperinsulinism
Keywords: hyperinsulinism
hypoglycemia
KATP channel
Kir6.2
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2007-12-12
Enrollment: 9
Sex: ALL
Minimum age (years): 7
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Blood Glucose Area Under the Curve (AUC 0-6h)
timeFrame: 6 hours
Secondary outcomes:
measure: Mean Plasma Insulin Area Under the Curve (AUC 0-6h)
timeFrame: 6 hours
measure: Mean Plasma Glucagon Area Under the Curve (AUC 0-6h)
timeFrame: 6 hours
measure: Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h)
timeFrame: 6 hours
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Diva D De Leon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.