Congenital HyperinsulinismPhase 1/2NCT00897676
Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
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.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- 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?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed diagnosis of hyperinsulinism
- Mutation analysis results demonstrating KATP channel defect
- Age 6 months to 18 years with
- Persistent hypoglycemia
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
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).
Read the 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.
- Conditions
- Congenital Hyperinsulinism
- Being tested
- Exendin-(9-39), placebo
- Keywords
- Hyperinsulinism, Hypoglycemia, KATP channel
- Medical subject headings
- Congenital Hyperinsulinism, Hyperinsulinism, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin-(9-39)Drug
100-500pmol/kg/min
placeboDrug
Also called (0.9% NaCl)
placebo (0.9% NaCl)
| Study group | Role | What they receive |
|---|---|---|
| Vehicle first, then Exendin-(9-39) | Other | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. Receives: Drug: Exendin-(9-39); Drug: placebo |
| Exendin-(9-39) first then Vehicle. | Other | An infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes.
. Receives: Drug: Exendin-(9-39); Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve (AUC) Plasma Glucose
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Measured: Time 0 min - time 360 min
Secondary outcomes (5)
Area Under the Curve (AUC) Plasma Insulin
Area under the curve plasma insulin from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
Measured: time 0 min to time 360 min
Area Under the Curve (AUC) Plasma C-peptide
Area under the curve plasma C-peptide from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Measured: time 0 min to time 360 min
Area Under the Curve (AUC) Plasma Glucagon
Area under the curve plasma glucagon from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Measured: time 0 min to time 360 min
Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
Area under the curve plasma total GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Measured: time 0 to time 360 min
Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
Area under the curve plasma active GLP-1 (glucagon-like peptide-1) from the beginning of the infusion of vehicle or exendin-(9-39) to the end of the infusion
Measured: time 0 min to time 360 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2009 (estimated)
- Study startMay 2009
- Primary completion26 Aug 2016
- Study completionJan 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 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)
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diva De Leon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Diva De Leon, Children's Hospital of Philadelphia
- Investigators
- Diva D DeLeon, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00897676
- Sponsor's protocol ID
- 2008-10-6255
- Other IDs
- R01FD004905
- Status last verified
- Mar 2020
- First submitted
- 8 May 2009
- Last updated
- 13 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 35416981
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity
- ClinicalTrials.gov ID
- NCT00897676
- Acronym / sponsor ID
- 2008-10-6255
- Conditions
- Congenital Hyperinsulinism
- Keywords
- Hyperinsulinism, Hypoglycemia, KATP channel
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Diva De LeonUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- 26 Aug 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 12 May 2009 (estimated)
- Results
- Posted 18 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- 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)
| Arm | Type | Receives |
|---|---|---|
| Vehicle first, then Exendin-(9-39) | Other | Drug: Exendin-(9-39), Drug: placeboAn infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). At time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. The following day, at time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. |
| Exendin-(9-39) first then Vehicle. | Other | Drug: Exendin-(9-39), Drug: placeboAn infusion of vehicle (0.9%NaCl) will run for 60 minutes(time -60 to 0) before starting the study infusion of vehicle or exendin-(9-39). . At time 0, exendin-(9-39) at a dose ranging from 100-500pmol/kg/min will be started and continue for 6 hours. The following day, at time 0, vehicle (0.9%NaCl) will be started and will continue for 6 hours. During both infusions, blood glucose, insulin, c-peptide, GLP-1, and glucagon will be measured every 30 minutes. . |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Confirmed diagnosis of hyperinsulinism
- Mutation analysis results demonstrating KATP channel defect
- Age 6 months to 18 years with
- Persistent hypoglycemia
Key exclusion criteria (4 listed)
- 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
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)100-500pmol/kg/min | Drug | Exendin-(9-39) first then Vehicle., Vehicle first, then Exendin-(9-39) |
| placeboAlso: (0.9% NaCl)placebo (0.9% NaCl) | Drug | Exendin-(9-39) first then Vehicle., Vehicle first, then Exendin-(9-39) |
Primary outcome
Area Under the Curve (AUC) Plasma Glucose
Time frame: Time 0 min - time 360 min
Area under the curve plasma glucose from the initiation of infusion of vehicle or exendin-(9-39) to end of the infusion
5 secondary outcomes
Area Under the Curve (AUC) Plasma Insulin
Time frame: time 0 min to time 360 min
Area Under the Curve (AUC) Plasma C-peptide
Time frame: time 0 min to time 360 min
Area Under the Curve (AUC) Plasma Glucagon
Time frame: time 0 min to time 360 min
Area Under the Curve ( AUC) Plasma Total GLP-1 (Glucagon-like Peptide-1)
Time frame: time 0 to time 360 min
Area Under the Curve ( AUC) Plasma Active GLP-1 (Glucagon-like Peptide-1)
Time frame: time 0 min to time 360 min
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35416981Stefanovski 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.
- 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 DeLeon, MD 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 13 Mar 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 18 Jan 2018). 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?
Area Under the Curve (AUC) Plasma Glucose (time frame: Time 0 min - time 360 min). 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 NCT00897676, which also lists 1 linked publication.
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 13 Mar 2020.