- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02524639
Sirolimus for the Treatment of Hyperinsulinism
Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism.
Study Overview
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 Type
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- The Children's Hospital of Philadelphia
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sirolimus
All enrolled subjects will receive Sirolimus 1 mg/m2/day twice a day for 6 weeks.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of children off intravenous dextrose support
Time Frame: 6 weeks
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in number hypoglycemic episodes per child per day
Time Frame: 6 weeks
|
6 weeks
|
Plasma insulin levels during fasting
Time Frame: 8 hours
|
8 hours
|
Number of participants with Adverse Events
Time Frame: 6 weeks
|
6 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15-011973
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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 Hyperinsulinism
-
University Hospital, Basel, SwitzerlandGottfried und Julia Bangerter-Rhyner-StiftungRecruitingEndogenous HyperinsulinismSwitzerland
-
University of Castilla-La ManchaEnrolling by invitationGlucose, High Blood | Exercise-Induced HyperinsulinismSpain
-
University Medicine GreifswaldCompletedNon-focal Congenital HyperinsulinismGermany
-
Elizabeth A RosenfeldNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University... and other collaboratorsCompletedHyperinsulinism-Hyperammonemia SyndromeUnited States
-
Children's Hospital of PhiladelphiaUniversity of Pennsylvania; Lawson Wilkins Pediatric Endocrine SocietyWithdrawn
-
Children's Hospital of PhiladelphiaUniversity of PennsylvaniaCompletedPersistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) | Congenital Hyperinsulinism (CHI)United States
-
Miguel PampaloniRecruitingCongenital HyperinsulinismUnited States
-
Zealand PharmaCompletedCongenital HyperinsulinismUnited States, United Kingdom, Germany, Israel
-
Montefiore Medical CenterNo longer availableCongenital HyperinsulinismUnited States
-
Diva De LeonTerminatedCongenital HyperinsulinismUnited States
Clinical Trials on Sirolimus
-
Aadi Bioscience, Inc.Approved for marketingTSC1 | TSC2 | PEComa, Malignant | mTOR Pathway Abberation
-
Johns Hopkins UniversityMacuSight, Inc.CompletedPanuveitis | Uveitis | Posterior Uveitis | Intermediate UveitisUnited States
-
Stefan Schieke MDWithdrawnCutaneous T-cell Lymphoma (CTCL)United States
-
Aadi Bioscience, Inc.CompletedHigh Grade Recurrent Glioma and Newly Diagnosed GlioblastomaUnited States
-
Brigham and Women's HospitalNational Heart, Lung, and Blood Institute (NHLBI)CompletedLymphangioleiomyomatosisUnited States
-
Xijing HospitalAir Force Military Medical University, China; Shanghai MicroPort Medical (Group)... and other collaboratorsUnknown
-
The University of Texas Health Science Center,...Society for Pediatric DermatologyCompletedTuberous Sclerosis | Neurofibromatoses | Neurofibroma | AngiofibromaUnited States
-
Meril Life Sciences Pvt. Ltd.Lifecare Institute of Medical Sciences and Research Ahmedabad Gujarat IndiaCompleted
-
Paul S Teirstein, MDCordis CorporationCompletedCoronary Artery Disease | Coronary Thrombosis | Coronary RestenosisUnited States
-
Shanghai Jiao Tong University School of MedicineUnknownCoronary Artery DiseaseChina