Clinical trial NCT00897676: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Congenital Hyperinsulinism
Keywords: Hyperinsulinism
Hypoglycemia
KATP channel
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2009-05-12
Enrollment: 17
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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)
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Area Under the Curve (AUC) Plasma Glucose
timeFrame: Time 0 min - time 360 min
Secondary outcomes:
measure: Area Under the Curve (AUC) Plasma Insulin
timeFrame: time 0 min to time 360 min
measure: Area Under the Curve (AUC) Plasma C-peptide
timeFrame: time 0 min to time 360 min
measure: Area Under the Curve (AUC) Plasma Glucagon
timeFrame: time 0 min to time 360 min
measure: Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
timeFrame: time 0 to time 360 min
measure: Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
timeFrame: time 0 min to time 360 min
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 DeLeon, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.