Sapropterin as a Treatment for Autistic Disorder: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Clinical Global Impression -- Improvement (CGI-I) Scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: sapropterin (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Clinical Global Impression -- Improvement (CGI-I) Scale
时间窗: Weekly for 4 weeks, then monthly, with 16-week end point. Primary outcome assessment used two time points, baseline and 16 weeks.
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
Clinical Global Impression -- Severity (CGI-S) Scale
时间窗: 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
次要结局
- 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)
- Aberrant Behavior Checklist (ABC) - Inappropriate Speech(Primary outcome assessment used two time points, baseline and 16 weeks.)
- Social Responsiveness Scale (SRS)(Primary outcome assessment used two time points, baseline and 16 weeks.)
- Parent Global Assessment (PGA) Scale(Baseline, 8 weeks, and 16 weeks)
研究者
Glen R. Elliott
Chief Psychiatrist and Medical Director
The Children's Health Council