Sirolimus for the Treatment of Hyperinsulinism

NCT02524639 | Withdrawn Phase 1

• 1 other identifier: 15-011973
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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 adenosine triphosphate-sensitive potassium (KATP) channels.

Conditions

Hyperinsulinism

Outcome Measures

Primary Outcomes (1)

• Number of children off intravenous dextrose support

  6 weeks

Secondary Outcomes (3)

• Change in number hypoglycemic episodes per child per day

  6 weeks

• Plasma insulin levels during fasting

  8 hours

• Number of participants with Adverse Events

  6 weeks

Study Arms (1)

Sirolimus

EXPERIMENTAL

All enrolled subjects will receive Sirolimus 1 mg/m2/day twice a day for 6 weeks.

Drug: Sirolimus

Interventions

Sirolimus DRUG

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.

Also known as: Rapamune

Sirolimus

Eligibility Criteria

• Age: Up to 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hyperinsulinism

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Diva De Leon, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: August 12, 2015
• First Posted: August 17, 2015
• Study Start: August 12, 2015
• Primary Completion: May 29, 2018
• Study Completion: May 29, 2018
• Last Updated: June 13, 2018

Record last verified: 2018-05

Locations

US (1)