Congenital HyperinsulinismPhase 1/2NCT00835328

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

A Phase 1/2 study testing Exendin (9-39) in people with Congenital Hyperinsulinism, run by Diva De Leon at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 12 months
Conditions the study is for: Congenital Hyperinsulinism
What is being tested?: Exendin (9-39)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 26 Aug 2009to 28 Jan 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 12 months
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including:
Treatment with glucagon 4 hours prior to infusion (T=0)
Treatment with octreotide 24 hours prior to infusion (T=0)
Treatment with diazoxide 72 hours prior to infusion (T=0)
Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.

Trial locations and contacts

1 site in 1 country.

United States1 site

The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Congenital Hyperinsulinism
Being tested: Exendin (9-39), Vehicle
Keywords: Congenital Hyperinsulinism, Hyperinsulinism, Hypoglycemia, KATP channel, Metabolic Diseases, Pancreatic Disease, Glucose Metabolism Disorders, Infant, Newborn, Diseases
Medical subject headings: Congenital Hyperinsulinism, Hyperinsulinism, Hypoglycemia, Metabolic Diseases, Pancreatic Diseases, Glucose Metabolism Disorders, Infant, Newborn, Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Exendin (9-39)Drug
A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.
VehicleDrug
Also called Placebo
A short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.

Study groups in NCT00835328
Study group	Role	What they receive
Exendin (9-39) 0.02 mg/kg/hr	Experimental	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. Receives: Drug: Exendin (9-39); Drug: Vehicle
Exendin (9-39) 0.04 mg/kg/hr	Experimental	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. Receives: Drug: Exendin (9-39); Drug: Vehicle
Exendin (9-39) 0.10 mg/kg/hr	Experimental	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. Receives: Drug: Exendin (9-39); Drug: Vehicle
Exendin (9-39) 0.20 mg/kg/hr	Experimental	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. Receives: Drug: Exendin (9-39); Drug: Vehicle

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Glucose Infusion Rate (GIR)
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.
Measured: Up to 9 hours after the initiation of infusion
To Determine the Pharmacokinetics of Exendin (9-39)
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.
Measured: Up to 12 hours after the initiation of infusion

Secondary outcomes (4)

Safety and Tolerability of Exendin (9-39)
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]
Measured: Up to 24 hours post-infusion
Mean Plasma Insulin
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.
Measured: Up to 9 hours after the initiation of infusion
Mean Plasma Glucose
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.
Measured: Up to 9 hours after the initiation of infusion
Mean Betahydroxybutyrate Levels
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.
Measured: Up to 12 hours after the initiation of infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Aug 200928 Jan 2017

First posted3 Feb 2009 (estimated)
Study start26 Aug 2009
Primary completion28 Jan 2017
Study completion28 Jan 2017

Why it stopped: Study stopped prematurely to test a new formulation of Exendin (9-39)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Congenital HyperinsulinismStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: This is a two-period, two-treatment cross-over clinical study with a dose-escalation component. Each subject, in random order, will receive an intravenous (IV) infusion of Exendin (9-39) and normal saline vehicle for up to 9 hours on two separate days.
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00835328
Sponsor's protocol ID: 2008-10-6256
Status last verified: May 2020
First submitted: 2 Feb 2009
Last updated: 1 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Congenital Hyperinsulinism trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Role of Glucagon-Like Peptide-1 (GLP-1) in Congenital Hyperinsulinism: Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia
ClinicalTrials.gov ID: NCT00835328
Acronym / sponsor ID: 2008-10-6256
Conditions: Congenital Hyperinsulinism
Keywords: Congenital Hyperinsulinism, Hyperinsulinism, Hypoglycemia, KATP channel, Metabolic Diseases, Pancreatic Disease, Glucose Metabolism Disorders, Infant, Newborn, Diseases
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study stopped prematurely to test a new formulation of Exendin (9-39)
Enrolment: 14 participants (actual)
Lead sponsor: Diva De LeonUniversity, hospital or other
Study start: 26 Aug 2009 (actual)
Primary completion: 28 Jan 2017 (actual)
Study completion: 28 Jan 2017 (actual)
First posted: 3 Feb 2009 (estimated)
Results: Posted 14 May 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4
Model description: This is a two-period, two-treatment cross-over clinical study with a dose-escalation component. Each subject, in random order, will receive an intravenous (IV) infusion of Exendin (9-39) and normal saline vehicle for up to 9 hours on two separate days.

Arm	Type	Receives
Exendin (9-39) 0.02 mg/kg/hr	Experimental	Drug: Exendin (9-39), Drug: VehicleCohort 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.
Exendin (9-39) 0.04 mg/kg/hr	Experimental	Drug: Exendin (9-39), Drug: VehicleCohort 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.
Exendin (9-39) 0.10 mg/kg/hr	Experimental	Drug: Exendin (9-39), Drug: VehicleCohort 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.
Exendin (9-39) 0.20 mg/kg/hr	Experimental	Drug: Exendin (9-39), Drug: VehicleCohort 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.

Who may qualify

Ages: Up to 12 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

Evidence of a medical condition that might alter results, including kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
Treatment with medications that may affect glucose metabolism at the time of initiation of study procedures, including:
Suspected Beckwith-Wiedemann syndrome or other syndromic forms of congenital hyperinsulinism.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Exendin (9-39)A short-term intravenous infusion of the investigational drug, Exendin (9-39), will be administered over up to 9 hours.	Drug	Exendin (9-39) 0.02 mg/kg/hr, Exendin (9-39) 0.04 mg/kg/hr, Exendin (9-39) 0.10 mg/kg/hr, Exendin (9-39) 0.20 mg/kg/hr
VehicleAlso: PlaceboA short-term intravenous infusion of normal saline (0.9% NaCl), or the vehicle, will be administered over up to 9 hours.	Drug	Exendin (9-39) 0.02 mg/kg/hr, Exendin (9-39) 0.04 mg/kg/hr, Exendin (9-39) 0.10 mg/kg/hr, Exendin (9-39) 0.20 mg/kg/hr

Primary outcome

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.
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.

4 secondary outcomes

Safety and Tolerability of Exendin (9-39)
Time frame: Up to 24 hours post-infusion
Mean Plasma Insulin
Time frame: Up to 9 hours after the initiation of infusion
Mean Plasma Glucose
Time frame: Up to 9 hours after the initiation of infusion
Mean Betahydroxybutyrate Levels
Time frame: Up to 12 hours after the initiation of infusion

Results and safety

Results posted to the registry on 14 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exendin (9-39) 0.02 mg/kg/hr	5	5
Exendin (9-39) 0.04 mg/kg/hr	0	0
Exendin (9-39) 0.10 mg/kg/hr	0	0
Exendin (9-39) 0.20 mg/kg/hr	0	0

Primary outcome: Mean Glucose Infusion Rate (GIR)

Time frame: Up to 9 hours after the initiation of infusion

Population analysed: Subjects served as their own control for comparison between the effects of Exendin (9-39) and the normal saline vehicle. The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.

Primary outcome: To Determine the Pharmacokinetics of Exendin (9-39)

Time frame: Up to 12 hours after the initiation of infusion

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Safety monitoring for adverse events will occur for 24-hours post study-drug infusion. For this study, the treatment follow-up period is defined by the half-life of the investigational product.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exendin (9-39) 0.02 mg/kg/hr	0 of 4 (0%)	1 of 5 (20%)	0 of 5
Exendin (9-39) 0.04 mg/kg/hr	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Exendin (9-39) 0.10 mg/kg/hr	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Exendin (9-39) 0.20 mg/kg/hr	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Vehicle	0 of 13 (0%)	10 of 13 (76.9%)	0 of 13

Limitations and caveats (from the sponsor): The trial was terminated after 14 participants enrolled in the study. No data is available for any outcome measures.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Diva D De Leon, MD MSCE principal investigator

Children's Hospital of Philadelphia

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Exendin (9-39) in people with Congenital Hyperinsulinism, run by Diva De Leon at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Glucose Infusion Rate (GIR) (time frame: Up to 9 hours after the initiation of infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00835328.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2020.