Clinical trial NCT00850070: Sapropterin as a Treatment for Autistic Disorder
Official title: Sapropterin as a Treatment for Autistic Disorder: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autistic Disorder
Keywords: autism
Lead sponsor: The Children's Health Council
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2009-02-24
Enrollment: 46
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Global Impression -- Improvement (CGI-I) Scale
timeFrame: Weekly for 4 weeks, then monthly, with 16-week end point. Primary outcome assessment used two time points, baseline and 16 weeks.
measure: Clinical Global Impression -- Severity (CGI-S) Scale
timeFrame: Baseline, 8 weeks, and 16 weeks. Primary outcome assessment used 2 time points, baseline and 16 weeks.
Secondary outcomes:
measure: Preschool Language Scale-Fourth Edition (PLS-4). Assesses Expressive and Receptive Language Skills in Ages Birth Through 6 Years, 11 Months.
timeFrame: Primary outcome assessment examined the difference in scores between baseline and week 16.
measure: Vineland Adaptive Behavior Scale-II.
timeFrame: Primary outcome assessment used two time points, baseline and 16 weeks.
measure: Children's Yale Brown Obsessive Compulsive Scale (C-YBOCS)
timeFrame: Baseline, 8 weeks, and 16 weeks
measure: Connor's Preschool ADHD Questionnaire
timeFrame: Baseline, 8 weeks, and 16 weeks
measure: Adverse Events Scale
timeFrame: Every 1-2 weeks for 16 weeks
measure: Aberrant Behavior Checklist (ABC) - Inappropriate Speech
timeFrame: Primary outcome assessment used two time points, baseline and 16 weeks.
measure: Social Responsiveness Scale (SRS)
timeFrame: Primary outcome assessment used two time points, baseline and 16 weeks.
measure: Parent Global Assessment (PGA) Scale
timeFrame: Baseline, 8 weeks, and 16 weeks
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: The Children's Health Council
state: California
Study officials:
affiliation: The Children's Health Council
name: Glen R Elliott, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klaiman C, Huffman L, Masaki L, Elliott GR. Tetrahydrobiopterin as a treatment for autism spectrum disorders: a double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2013 Jun;23(5):320-8. doi: 10.1089/cap.2012.0127.