Sirolimus for the Treatment of Hyperinsulinism
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism.|
- Number of children off intravenous dextrose support [ Time Frame: 6 weeks ]
- 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 ]
|Study Start Date:||August 2015|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
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 Name: Rapamune
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02524639
|Contact: Diva De Leon, MD||215-590-3420||Deleon@email.chop.edu|
|Contact: Jamie Koh, RNfirstname.lastname@example.org|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Diva De Leon, MD 215-590-3420 email@example.com|
|Contact: Katherine Lord, MD 610-888-9161 firstname.lastname@example.org|
|Sub-Investigator: Katherine Lord, MD|
|Principal Investigator:||Diva De Leon, MD||Children's Hospital of Philadelphia|