- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00850070
Sapropterin as a Treatment for Autistic Disorder
April 27, 2018 updated by: Glen R. Elliott, The Children's Health Council
Sapropterin as a Treatment for Autistic Disorder: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
46
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Palo Alto, California, United States, 94304
- The Children's Health Council
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 years to 6 years (CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: sapropterin, 100 mg capsules
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.
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Patients will receive sapropterin 20 mg per kilogram per day for 16 weeks
Other Names:
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PLACEBO_COMPARATOR: Placebo, matching active drug
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.
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Patients will receive a placebo identical in form and dosage to the active drug daily for 16 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impression -- Improvement (CGI-I) Scale
Time Frame: Weekly for 4 weeks, then monthly, with 16-week end point. Primary outcome assessment used two time points, baseline and 16 weeks.
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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
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Weekly for 4 weeks, then monthly, with 16-week end point. Primary outcome assessment used two time points, baseline and 16 weeks.
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Clinical Global Impression -- Severity (CGI-S) Scale
Time Frame: Baseline, 8 weeks, and 16 weeks. Primary outcome assessment used 2 time points, baseline and 16 weeks.
|
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
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Baseline, 8 weeks, and 16 weeks. Primary outcome assessment used 2 time points, baseline and 16 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Preschool Language Scale-Fourth Edition (PLS-4). Assesses Expressive and Receptive Language Skills in Ages Birth Through 6 Years, 11 Months.
Time Frame: Primary outcome assessment examined the difference in scores between baseline and week 16.
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Measures expressive & receptive language and total scores in ages birth to 6 years 11 months.
The scales generate raw, standard, and age-equivalent scores; raw scores for the total scale were selected for use in this study.
Total is average of subscales.
Minimum raw score = 0, maximum = 130.
Higher scores indicate better language abilities.
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.
For the outcome effect, the difference between baseline and 16 weeks was determined as an indicator for change.
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Primary outcome assessment examined the difference in scores between baseline and week 16.
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Vineland Adaptive Behavior Scale-II.
Time Frame: Primary outcome assessment used two time points, baseline and 16 weeks.
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the Vineland-2 is a semi-structured interview designed to assess communicatino, daily living, socialization and motor skills.
The Vineland-2 is comprised of a total Adaptive Composite scale; we chose to use 10 subscales that specifically address functional domains relevant for a young ASD sample - Receptive Communication, Expressive Communication, Personal Daily Living Skills, Domestic Daily Living Skills, Community Daily Living Skills, Interpersonal Relations, Play Skills, Coping Skills, Gross Motor Skills, Fine Motor Skills.
Scales generate raw or sum, V-, and age-equivalent scores; raw scores were selected for use in the study.
Raw score ranges from 0 to 108 depending on the scale.
Total raw scale range is from 0 to 766.
Subscale scores are averaged to create the total adaptive behavior composite.
Higher subscale scores indicate more skills.
Difference between baseline and week 16 was used as an indicator of change.
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Primary outcome assessment used two time points, baseline and 16 weeks.
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Children's Yale Brown Obsessive Compulsive Scale (C-YBOCS)
Time Frame: Baseline, 8 weeks, and 16 weeks
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The C-YBOCS is a scale is designed to rate the severity of obsessive and compulsive symptoms in children and adolescents, ages 6 to 17 years.
It can be administered by a clinican or trained interviewer in a semi-structured fashion.
In general, the ratings depend on the child's and parent's report; however, the final rating is based on the clinical judgement of the interviewer.
Rate the characteristics of each item over the prior week up until, and including, the time of the interview.
Scores should reflect the average of each item for the entire week, unless otherwise specified.
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Baseline, 8 weeks, and 16 weeks
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Connor's Preschool ADHD Questionnaire
Time Frame: Baseline, 8 weeks, and 16 weeks
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Conners Early Childhood, addresses child behavior for ages 2 years to 6 years with a variety of scales, including an ADHD subdomain.
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Baseline, 8 weeks, and 16 weeks
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Adverse Events Scale
Time Frame: Every 1-2 weeks for 16 weeks
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This was not a standardized scale but a set of questions that was asked of each family - some standard and others open ended.
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Every 1-2 weeks for 16 weeks
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Aberrant Behavior Checklist (ABC) - Inappropriate Speech
Time Frame: Primary outcome assessment used two time points, baseline and 16 weeks.
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Subscale assessing echolalia & other odd speech.
Higher subscale scores indicate more symptoms.
4 items comprise the subscale, with range of scores from 0-4.
Total score range on this subscale is 0 to 16. Scores are averaged to compute overall score.
Difference in scores between baseline and week 16 were used as indicator of change.
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Primary outcome assessment used two time points, baseline and 16 weeks.
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Social Responsiveness Scale (SRS)
Time Frame: Primary outcome assessment used two time points, baseline and 16 weeks.
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The SRS is a 65-item scale used to measure the severity of symptoms in ASD as they occur in natural social settings.
The SRS is comprised of 1 Total scale and 5 subscales that generate raw scores that can be converted to standard T-scores (with mean of 50 and standard deviation of 10) for gender and rater type; standard scores were selected for use in this study.
A total T-score of 76 or higher is considered severe and strongly associated with a clinical diagnosis of autistic disorder.
A t-score of 60-75 is in the mild to moderate range and considered typical for children with mild or 'high-functioning' ASD, while a T-score of 59 or less suggests an absence of ASD symptoms.
A total raw score of >75 were associated with a sensitivity value of .85 and a specificity value of .75 for ASD.
Difference in scores between baseline and week 16 were used as an indicator of change.
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Primary outcome assessment used two time points, baseline and 16 weeks.
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Parent Global Assessment (PGA) Scale
Time Frame: Baseline, 8 weeks, and 16 weeks
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This is a measure where parents rate their impression of their child's improvement, in a global manner.
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Baseline, 8 weeks, and 16 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Glen R Elliott, Ph.D., M.D., The Children's Health Council
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2009
Primary Completion (ACTUAL)
August 1, 2011
Study Completion (ACTUAL)
October 1, 2011
Study Registration Dates
First Submitted
February 20, 2009
First Submitted That Met QC Criteria
February 23, 2009
First Posted (ESTIMATE)
February 24, 2009
Study Record Updates
Last Update Posted (ACTUAL)
May 1, 2018
Last Update Submitted That Met QC Criteria
April 27, 2018
Last Verified
April 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHC-0901
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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