HyperinsulinismPhase 1/2NCT02524639
Sirolimus for the Treatment of Hyperinsulinism
A Phase 1/2 study testing Sirolimus in people with Hyperinsulinism, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
The purpose of this pilot study is to generate data to assess feasibility of study design/procedures and for formal sample size estimation for a larger multicenter study of the efficacy and safety of sirolimus in infants with medically-unresponsive congenital hyperinsulinism (HI) due to inactivating mutations of… Read more about this study
- Who is it for?
- Ages Up to 12 months
- Conditions the study is for
- Hyperinsulinism
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2015to 29 May 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Males or females age ≥14 days to 12 months.
- Confirmed diagnosis of hyperinsulinism.
- Mutation analysis results demonstrating bi-allelic mutations in either ABCC8 or KCNJ11.
- Failure to respond to maximal dose of diazoxide (15 mg/kg/day), if diazoxide is indicated.
- Unable to wean intravenous dextrose after at least 3 days of diazoxide therapy and/or
- Persistent hypoglycemia after at least 3 days of diazoxide therapy
- High glucose infusion rate requirement (greater or equal to 10 mg/kg/min).
- Parental/guardian permission (informed consent).
Who cannot join
- Infants with suspected or confirmed focal hyperinsulinism who are candidates for surgical resection
- Current therapy with diazoxide. Subjects may be eligible for participation 48 hrs after discontinuation of diazoxide.
- Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary, or renal disease:
- AST/SGOT > 2.5 times the upper limit of normal
- ALT/SGPT > 2.5 times the upper limit of normal
- Total bilirubin > 2.5 times the upper limit of normal
Show all 21Show fewer
- Hemoglobin < 9 gm/dL
- White blood cell count < 3,000/ mm3
- Platelet count < 100,000/mm3
- Creatinine > 2.5 times the upper limit of normal
- Evidence of active infection.
- Evidence of cardiac or respiratory failure.
- Known immune deficiency.
- Preterm (< 37 week gestation at birth).
- Treatment with immunosuppressants.
- Treatment with any drug known to interact significantly with sirolimus (strong inducers and strong inhibitors of CYP3A4 and P-gp with risk category D and X) including:
- Cyclosporine, clozapine, conivaptan, crizotinib, dabrafenib, dipyrone, boceprevir, echinacea, efavirenz, enzalutamide, fluconazole, fosphenytoin, fusidic acid, idelalisib, leflunomide, lomitapide, mifepristone, mitotane, natalizumab, nelfinavir, phenytoin, pimecrolimus, pimozide, posaconazole, roflumilast, St Johns Wort, stiripentol, tacrolimus, telaprevir, tofacitinib, rifampin, rifabutin, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin
- Any investigational drug use within 5 half-lives of the drug prior to initiation of therapy.
- Subjects who had participated in other investigational drug studies will be eligible to participate after 5 half-lives from the last dose of the investigational agent and have recovered from acute investigational agent associated toxicity
- History of surgical procedure within 8 weeks of enrollment.
- Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
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: Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism.
The purpose of this pilot study is to generate data to assess feasibility of study design/procedures and for formal sample size estimation for a larger multicenter study of the efficacy and safety of sirolimus in infants with medically-unresponsive congenital hyperinsulinism (HI) due to inactivating mutations of adenosine triphosphate-sensitive potassium (KATP) channels.
Read the detailed description
Treatment options for children with diffuse adenosine triphosphate-sensitive potassium (KATP) channel hyperinsulinism (KATPHI) are limited and most of them require a near-total pancreatectomy to control the hypoglycemia. However, at least 40% of these children continue to have persistent hypoglycemia after surgery and their long-term outcomes are complicated by the development of diabetes.
There is evidence that suggests that mammalian target of rapamycin (mTOR) inhibitors are useful in controlling the hypoglycemia in hyperinsulinemic hypoglycemia. But before adapting this as standard therapy for children with hyperinsulinism, a carefully controlled study of the efficacy and safety of sirolimus for hyperinsulinism is clearly needed.
Sirolimus is an mTOR inhibitor, which is FDA-approved for the prophylaxis of organ rejection in patients age 13 years and older receiving kidney transplantation. This is an open label pilot study to assess the effect, safety and tolerability of sirolimus in infants with diazoxide-unresponsive HI due to mutations in the genes encoding the KATP channels. Subjects will be treated with sirolimus for 6 weeks.
- Conditions
- Hyperinsulinism
- Being tested
- Sirolimus
- Medical subject headings
- Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
Subjects will receive 1 mg/m2/day orally for 6 weeks. Maintenance dose will be titrated up or down by 0.25-0.5 mg/m2/day every 4 days. Serum concentration will be checked on day 4 after initial therapy and 4 days after any dose adjustment. Levels will be checked at lease once a week during the duration of the study. Target serum concentration range is 5-10 ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | All enrolled subjects will receive Sirolimus 1 mg/m2/day twice a day for 6 weeks. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of children off intravenous dextrose support
Measured: 6 weeks
Secondary outcomes (3)
Change in number hypoglycemic episodes per child per day
Measured: 6 weeks
Plasma insulin levels during fasting
Measured: 8 hours
Number of participants with Adverse Events
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study start12 Aug 2015 (estimated)
- Primary completion29 May 2018
- Study completion29 May 2018
Why it stopped: Due to strict inclusion and exclusion criteria no subjects were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperinsulinismStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Diva De Leon, Children's Hospital of Philadelphia
- Investigators
- Diva De Leon, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02524639
- Sponsor's protocol ID
- 15-011973
- Status last verified
- May 2018
- First submitted
- 12 Aug 2015
- Last updated
- 13 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism.
- ClinicalTrials.gov ID
- NCT02524639
- Acronym / sponsor ID
- 15-011973
- Conditions
- Hyperinsulinism
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to strict inclusion and exclusion criteria no subjects were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- 12 Aug 2015 (estimated)
- Primary completion
- 29 May 2018 (actual)
- Study completion
- 29 May 2018 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Not posted in the source record
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 pilot study is to generate data to assess feasibility of study design/procedures and for formal sample size estimation for a larger multicenter study of the efficacy and safety of sirolimus in infants with medically-unresponsive congenital hyperinsulinism (HI) due to inactivating mutations of adenosine triphosphate-sensitive potassium (KATP) channels.
Detailed description
Treatment options for children with diffuse adenosine triphosphate-sensitive potassium (KATP) channel hyperinsulinism (KATPHI) are limited and most of them require a near-total pancreatectomy to control the hypoglycemia. However, at least 40% of these children continue to have persistent hypoglycemia after surgery and their long-term outcomes are complicated by the development of diabetes.
There is evidence that suggests that mammalian target of rapamycin (mTOR) inhibitors are useful in controlling the hypoglycemia in hyperinsulinemic hypoglycemia. But before adapting this as standard therapy for children with hyperinsulinism, a carefully controlled study of the efficacy and safety of sirolimus for hyperinsulinism is clearly needed.
Sirolimus is an mTOR inhibitor, which is FDA-approved for the prophylaxis of organ rejection in patients age 13 years and older receiving kidney transplantation. This is an open label pilot study to assess the effect, safety and tolerability of sirolimus in infants with diazoxide-unresponsive HI due to mutations in the genes encoding the KATP channels. Subjects will be treated with sirolimus for 6 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusAll enrolled subjects will receive Sirolimus 1 mg/m2/day twice a day for 6 weeks. |
Who may qualify
- Ages
- Up to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Males or females age ≥14 days to 12 months.
- Confirmed diagnosis of hyperinsulinism.
- Mutation analysis results demonstrating bi-allelic mutations in either ABCC8 or KCNJ11.
- Failure to respond to maximal dose of diazoxide (15 mg/kg/day), if diazoxide is indicated.
- High glucose infusion rate requirement (greater or equal to 10 mg/kg/min).
Key exclusion criteria (21 listed)
- Infants with suspected or confirmed focal hyperinsulinism who are candidates for surgical resection
- Current therapy with diazoxide. Subjects may be eligible for participation 48 hrs after discontinuation of diazoxide.
- Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary, or renal disease:
- Evidence of active infection.
- Evidence of cardiac or respiratory failure.
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 |
|---|---|---|
| SirolimusAlso: RapamuneSubjects will receive 1 mg/m2/day orally for 6 weeks. Maintenance dose will be titrated up or down by 0.25-0.5 mg/m2/day every 4 days. Serum concentration will be checked on day 4 after initial therapy and 4 days after any dose adjustment. Levels will be checked at lease once a week during the duration of the study. Target serum concentration range is 5-10 ng/mL. | Drug | Sirolimus |
Primary outcome
Number of children off intravenous dextrose support
Time frame: 6 weeks
3 secondary outcomes
Change in number hypoglycemic episodes per child per day
Time frame: 6 weeks
Plasma insulin levels during fasting
Time frame: 8 hours
Number of participants with Adverse Events
Time frame: 6 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
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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 De Leon, 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 Sirolimus in people with Hyperinsulinism, run by Children's Hospital of Philadelphia 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 8 inclusion and 21 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: withdrawn, as of the sponsor's last update on 13 Jun 2018. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of children off intravenous dextrose support (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2018.