Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia

May 16, 2020 updated by: Diva De Leon

Role of Glucagon-Like Peptide-1 (GLP-1) in Congenital Hyperinsulinism: Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia

The primary aim of this study is to evaluate the effect of Exendin (9-39) on glucose requirements to maintain euglycemia in pediatric patients with congenital hyperinsulinism (CHI) who have failed medical therapy. The secondary aims are to determine the therapeutic plasma levels, plasma half-life and pharmacokinetics of Exendin (9-39) during a 9-hour intravenous infusion.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will enroll infants with congenital hyperinsulinism owing to KATP channel mutations who are unresponsive to medical therapy and will require a pancreatectomy to control hypoglycemia from a single academic medical center in the United States.

An open-label, two-period, two-treatment crossover study design with a dose-escalation component will be implemented. Successive cohorts of patients (up to 5 participants/cohort) will each receive a fixed dose of Exendin (9-39) infusion and normal saline vehicle on two separate days in random order. The protocol specifies 0.02 mg/kg/hr, via continuous intravenous infusion, administered over 9-hours for the first cohort. The volume of saline to be infused will be calculated to match the volume of Exendin (9-39). Successive cohorts will be given doses that are increased in up to 1/2 log increments. Overall, the investigators hypothesize that antagonism of the GLP-1 receptor by Exendin (9-39) will increase fasting blood glucose levels, prevent protein-induced hypoglycemia and decrease glucose requirement to maintain euglycemia in infants with CHI.

Aim 1. To examine the effect of Exendin (9-39) on glucose requirements to maintain euglycemia in infants with congenital hyperinsulinism unresponsive to medical therapy.

Aim 2. To determine therapeutic plasma levels, plasma half-life and pharmacokinetics of Exendin-(9-39) during an intravenous infusion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed clinical diagnosis of congenital hyperinsulinism
  2. Infants less than 12 months of age at study enrollment
  3. Failure to respond to treatment with diazoxide

Exclusion Criteria:

  1. Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure

  2. Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including:

    1. Treatment with glucagon 4 hours prior to infusion (T=0)
    2. Treatment with octreotide 24 hours prior to infusion (T=0)
    3. Treatment with diazoxide 72 hours prior to infusion (T=0)
  3. Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Exendin (9-39) 0.02 mg/kg/hr
Cohort 1: Participants will be administered 0.02 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Drug: Exendin (9-39)
A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.
Drug: Vehicle
A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.
Other Names:
  • Placebo
Experimental: Exendin (9-39) 0.04 mg/kg/hr
Cohort 2: Participants will be administered 0.04 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Drug: Exendin (9-39)
A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.
Drug: Vehicle
A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.
Other Names:
  • Placebo
Experimental: Exendin (9-39) 0.10 mg/kg/hr
Cohort 3: Participants will be administered 0.10 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 6 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Drug: Exendin (9-39)
A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.
Drug: Vehicle
A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.
Other Names:
  • Placebo
Experimental: Exendin (9-39) 0.20 mg/kg/hr
Cohort 4: Participants will be administered 0.20 mg/kg/hr of Exendin (9-39) and vehicle (normal saline), via continuous intravenous infusion, over 9 hours on two separate days in random order, with 3 hours of follow-up after the last dose is administered or until blood glucose is < 70 mg/dL (whichever comes first). Glucose infusion rates (GIR) will be titrated three hours prior to infusions to keep blood glucose in the range of 70-90 mg/dL. During both infusions, blood glucose will be measured every 30 minutes.
Drug: Exendin (9-39)
A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.
Drug: Vehicle
A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Glucose Infusion Rate (GIR)
Time Frame: Up to 9 hours after the initiation of infusion
To assess the effect of Exendin (9-39) on glucose infusion rate, glucose infusion rate (GIR) over the last 2 hours of the treatment period was calculated by adding the total amount of intravenous glucose (mg) received over 2 hours divided by the weight (kg) and by time (120 min) during infusion of Exendin (9-39) and normal saline vehicle.
Up to 9 hours after the initiation of infusion
To Determine the Pharmacokinetics of Exendin (9-39)
Time Frame: Up to 12 hours after the initiation of infusion
The following PK variables of interest include AUC0-∞, AUC0-t, maximal concentration (Cmax), time to maximal concentration (Tmax), concentration at end of infusion (Ceoi), steady state volume of distribution (Vss), clearance (CL) and half-life (t1/2) of Exendin (9-39). These will be derived through both non-compartmental and model-based methods.
Up to 12 hours after the initiation of infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of Exendin (9-39)
Time Frame: Up to 24 hours post-infusion
Number of participants with adverse events as a measure of safety and tolerability [evaluated by the result of laboratory safety tests (hematology, chemistry, urinalysis), vital signs, physical examinations, and 12-lead ECG]
Up to 24 hours post-infusion
Mean Plasma Insulin
Time Frame: Up to 9 hours after the initiation of infusion
To assess the effect of Exendin (9-39) on plasma insulin levels, samples were collected at various time points during the infusion [Exendin (9-39) or vehicle] including: at the start of the infusion (T=0) and at 1, 5, and 9 hours post initiation of the infusion.
Up to 9 hours after the initiation of infusion
Mean Plasma Glucose
Time Frame: Up to 9 hours after the initiation of infusion
To assess the effect of Exendin (9-39) on plasma glucose levels, samples were collected at various time points during the infusion [Exendin (9-39) or vehicle] including: at the start of the infusion (T=0) and at 1, 5, and 9 hours post initiation of the infusion.
Up to 9 hours after the initiation of infusion
Mean Betahydroxybutyrate Levels
Time Frame: Up to 12 hours after the initiation of infusion
To assess the effect of Exendin (9-39) on mean betahydroxybutyrate levels, samples were collected at various time points during the infusion [Exendin (9-39) or vehicle] including: at the start of the infusion (T=0) and hourly up to 12-hours post initiation of the infusion.
Up to 12 hours after the initiation of infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Diva De Leon

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Diva D De Leon, MD MSCE, Children's Hospital of Philadelphia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 26, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 28, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 28, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 2, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 3, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2008-10-6256

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Congenital Hyperinsulinism

Clinical Trials on Exendin (9-39)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings