Sapropterin as a Treatment for Autistic Disorder

The Children's Health Council

Status and phase: Completed; Phase 2

Conditions: Autistic Disorder

Treatments: Drug: sapropterin; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00850070

CHC-0901

Details and patient eligibility

About

This study is intended to provide a definitive test of the hypothesis that elevating sapropterin (tetrahydrobiopterin, a cofactor for several key brain enzymes)concentrations in the CNS will result in measurable improvements in core symptoms of autism in young individuals, under age 6 years. The study will entail a double-blind, placebo-controlled 16-week intervention.

Full description

Over the past 20 years, several studies have suggested that sapropterin (tetrahydrobiopterin) might ameliorate core symptoms of autism at least in young (under age 6) subjects. However, those studies had somewhat questionable methodologies, a major one being that the doses of sapropterin used were roughly one tenth that thought to be needed to provide physiologically meaningful increases of sapropterin in the central nervous system (CNS). This study will look at the impact of a sustained exposure to this higher dose in well-diagnosed young children with autism.

Enrollment: 46 patients

Sex: All

Ages: 3 to 6 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Parents sign informed consent
• Child meets criteria for autistic disorder (based on score on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), given by a certified administrator, research reliable)
• Child has a Developmental Quotient (DQ) ≥ 50 (Vineland Adaptive Scales, Interview Edition)
• Parents agree to delay initiation of other treatments during double-blind trial

Exclusion criteria

• Child has had seizures in past 6 months or a change in seizure medications in past 4 weeks.
• Child has > 18 points on subscale of (Autism Behavior Checklist) ABC-I
• Child is taking any psychoactive medication other than supplements, anticonvulsants, or soporifics (melatonin, diphenhydramine)
• Child has had any change in standing medications in the past 4 weeks.
• Child has known genetic disorders
• Child has known severe neurological disorders, including cerebral palsy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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46 participants in 2 patient groups, including a placebo group

sapropterin, 100 mg capsules

Experimental group

Description:

Sapropterin was supplied as a 100 mg tablet and dosage was based on 20 mg/kg/d, rounding to the nearest 100 mg. Most subjects crushed the tablets and administered it in liquid or a food to mask the taste. Subjects took the same dose daily for 16 weeks.

Treatment:

Drug: sapropterin

Placebo, matching active drug

Placebo Comparator group

Description:

The placebo was supplied as a 100 mg tablet, and dosage was based on 20 mg/kg/d, rounding to the nearest 100 mg. Most subjects crushed the tablets and administered it in liquid or a food to mask the taste. Subjects took the same dose daily for 16 weeks.

Treatment:

Drug: Placebo