Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00571324
Other study ID # 2007-1-5131
Secondary ID R03DK078535-01
Status Completed
Phase Phase 1/Phase 2
First received December 10, 2007
Last updated November 9, 2017
Start date August 2007
Est. completion date December 2014

Study information

Verified date November 2017
Source Children's Hospital of Philadelphia
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 9
Est. completion date December 2014
Est. primary completion date December 2014
Accepts healthy volunteers No
Gender All
Age group 7 Years to 60 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Exendin-(9-39)
A short term intravenous infusion of the study drug, exendin-(9-39), will be given over 6 hours.
Other:
Vehicle
A short term intravenous infusion of normal saline, or the vehicle, will be given over 6 hours.

Locations

Country Name City State
United States The Children's Hospital of Philadelphia Philadelphia Pennsylvania

Sponsors (3)

Lead Sponsor Collaborator
Diva De Leon National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Mean Plasma Insulin Area Under the Curve (AUC 0-6h) 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. 6 hours
Secondary Mean Plasma Glucagon Area Under the Curve (AUC 0-6h) 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. 6 hours
Secondary Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h) 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. 6 hours
See also
  Status Clinical Trial Phase
Recruiting NCT02021604 - Fluorodopa F 18 in Congenital Hyperinsulinism and Insulinoma Phase 1
Recruiting NCT04732416 - HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) Phase 2
Completed NCT02937558 - CSI-Glucagon for Prevention of Hypoglycemia in Children With Congenital Hyperinsulinism Phase 2
Completed NCT02604485 - A Single-Dose Open-Label Study of XOMA 358 in Subjects With Congenital Hyperinsulinism Phase 2
Recruiting NCT04205604 - 18FluoroLDOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism Phase 2
Completed NCT00987168 - Sandostatine® LP and Hyperinsulinism Phase 2
Completed NCT00897676 - Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity Phase 1/Phase 2
Active, not recruiting NCT03941236 - Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 3
Completed NCT03042416 - 18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety Phase 3
Completed NCT04172441 - Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 2/Phase 3
Recruiting NCT04706910 - 18F-DOPA II - PET Imaging Optimization Phase 3
Recruiting NCT06208215 - RZ358 Treatment for Congenital Hyperinsulinism Phase 3
Completed NCT03777176 - A Two-Period Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism Phase 3
Recruiting NCT03768518 - GLP-1 Receptor Expression in CHI
Completed NCT04538989 - An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism Phase 2
Completed NCT01070758 - Lanreotide Autogel Treatment of Patients With Congenital Hyperinsulinism of Infancy Phase 4
Completed NCT00674440 - Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism Phase 2
Terminated NCT00835328 - Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia Phase 1/Phase 2
Withdrawn NCT03053284 - Pasireotide in Hyperinsulinemic Hypoglycemia Phase 2
No longer available NCT02835131 - Compassionate Use of SOM230 for Hyperinsulinemic/Hypoglycemia