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Trial record 4 of 17 for:    "Persistent Hyperinsulinemia Hypoglycemia of Infancy" OR "familial hyperinsulinism"

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

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Diva De Leon, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00571324
First received: December 10, 2007
Last updated: September 22, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Congenital Hyperinsulinism
Drug: Exendin-(9-39)
Other: Vehicle
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Mean Blood Glucose Area Under the Curve (AUC 0-6h) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Mean Plasma Insulin Area Under the Curve (AUC 0-6h) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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.

  • Mean Plasma Glucagon Area Under the Curve (AUC 0-6h) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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.

  • Mean Plasma Intact Glucagon-Like Peptide-1 (GLP-1) Area Under the Curve (AUC 0-6h) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    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.


Enrollment: 9
Study Start Date: August 2007
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exendin-(9-39) first, the Vehicle
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)
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.
Other Name: Placebo
Placebo Comparator: Vehicle first, then Exendin-(9-39)
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)
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.
Other Name: Placebo

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

Ages Eligible for Study:   7 Years to 60 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571324

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Diva De Leon
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Diva D De Leon, MD Children's Hospital of Philadelphia
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Diva De Leon, M.D. Assistant Professor of Pediatrics, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00571324     History of Changes
Other Study ID Numbers: 2007-1-5131  R03DK078535-01 
Study First Received: December 10, 2007
Results First Received: July 29, 2016
Last Updated: September 22, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital of Philadelphia:
hyperinsulinism
hypoglycemia
KATP channel
Kir6.2

Additional relevant MeSH terms:
Congenital Hyperinsulinism
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 07, 2016