Sapropterin as a Treatment for Autistic Disorder

NCT00850070 | Completed Phase 2 Results DMC

• 1 other identifier: CHC-0901
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Autistic Disorder

Keywords

autism

Outcome Measures

Primary Outcomes (2)

• Clinical Global Impression -- Improvement (CGI-I) Scale

  The CGI-I assessed the number of participants showing much or very much improvement on the CGI-I scale. This is a summary judgment made by a trained clinician based on observed and reported behaviors of the child compared to baseline. It is a 7-point scale from very much worse (1) to very much improved (7). Chi-square analyses were used to assess change in CHI-I scores (by group, post-test). Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time

  Weekly for 4 weeks, then monthly, with 16-week end point. Primary outcome assessment used two time points, baseline and 16 weeks.

• Clinical Global Impression -- Severity (CGI-S) Scale

  The CGI-S assessed the number of participants with improved severity illness on the CGI-S scale. This is a summary judgment made by a trained clinician of symptom severity. It is a 7-point scale that rates the severity of the patient's illness at time of assessment with 1 - normal, not at all, to 7 - extremely ill. Mixed-effects regression models via SPSS MIXED determined the main effects attributed to differences by group (BH4 and placebo), time (treated as categorical at levels baseline, 8 weeks, and 16 weeks) and the group-by-time interaction. We used random intercept and trend modeling that accounts for each individual's initial level of symptom severity/functioning and rate of change/time

  Baseline, 8 weeks, and 16 weeks. Primary outcome assessment used 2 time points, baseline and 16 weeks.

Secondary Outcomes (8)

• Preschool Language Scale-Fourth Edition (PLS-4). Assesses Expressive and Receptive Language Skills in Ages Birth Through 6 Years, 11 Months.

  Primary outcome assessment examined the difference in scores between baseline and week 16.

• Vineland Adaptive Behavior Scale-II.

  Primary outcome assessment used two time points, baseline and 16 weeks.

• Children's Yale Brown Obsessive Compulsive Scale (C-YBOCS)

  Baseline, 8 weeks, and 16 weeks

• Connor's Preschool ADHD Questionnaire

  Baseline, 8 weeks, and 16 weeks

• Adverse Events Scale

  Every 1-2 weeks for 16 weeks

Study Arms (2)

sapropterin, 100 mg capsules

EXPERIMENTAL

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.

Drug: sapropterin

Placebo, matching active drug

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

sapropterin DRUG

Patients will receive sapropterin 20 mg per kilogram per day for 16 weeks

Also known as: Kuvan, tetrahydrobiopterin

sapropterin, 100 mg capsules

Placebo DRUG

Patients will receive a placebo identical in form and dosage to the active drug daily for 16 weeks.

Also known as: sugar pill

Placebo, matching active drug

Eligibility Criteria

• Age: 3 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Children's Health Council: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

The Children's Health Council

Palo Alto, California, 94304, United States

Location

Related Publications (1)

• 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.

  PMID: 23782126 RESULT

MeSH Terms

Conditions

Autistic Disorder

Interventions

sapropterin; Sugars

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Glen R. Elliott, Ph.D., M.D.
• Organization: The Children's Health Council

gelliott@chconline.org

650.688.3649

Study Officials

• Glen R Elliott, Ph.D., M.D.

  The Children's Health Council

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Psychiatrist and Medical Director

Study Record Dates

• First Submitted: February 20, 2009
• First Posted: February 24, 2009
• Study Start: March 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: October 1, 2011
• Last Updated: May 1, 2018
• Results First Posted: February 28, 2014

Record last verified: 2018-04

Locations

US (1)