Biomarkers of Central Nervous System Tetrahydrobiopterin Concentration and Response to Tetrahydrobiopterin Supplementation in Children With Idiopathic Cognitive Developmental Disorders
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Preschool Language Scales
研究概览
简要总结
The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
详细描述
SUMMARY
PURPOSE: The purpose of this study is to develop biomarkers for central nervous system BH4 concentration in children with autism so they can be easily screened to determine if they may benefit from BH4 supplementation. Kuvan is a synthetic form of BH4. BH4 is an enzyme cofactor that is essential for several critical metabolic functions.
Procedures: Consented subjects' behavior, particularly irritability, cognitive and language function will be assessed at baseline to make sure that the subject meets the inclusion and exclusion criteria. Parents of subjects will be instructed to give the subjects 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast. Subjects will not be permitted to start any new supplement treatments during the study period but will be allowed to continue previous supplements. Subjects will be permitted to take over the counter medications or other prescription medications for acute illnesses. Evaluation of subjects will include three clinic visits for neuropsychological and clinical testing, completion of study-related questionnaires and telephone follow-up visits.
Course of Study: Subjects will be in the study for up to 16 weeks.
Enrollment: The study will enroll 20 (male and female) subjects, 2-6 years old, with delays in language and/or social development. Vulnerable populations include children. A pediatric risk assessment was completed by Ian Butler, MD with an outcome of minimum risks to subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children 2 years 0 months to 6 years 11 months of age will be recruited.
- •Delay in language and/or social development with or without delays in gross and/or fine motor development.
- •CSF BH4 level less than or equal to 30 nM/L as determined by lumbar puncture.
- •Adaptive Behavior greater than 50 as determined by the Vineland Adaptive Behavior Scale.
排除标准
- •Epilepsy / Seizure disorder as determined by medical history.
- •Epileptiform discharges without clinical seizures.
- •Metabolic disorder that would be a contraindication to tetrahydrobiopterin treatment.
- •Genetic disorder
- •Therapies that cannot be maintained at a constant level or have not been ongoing for more than 3 months as determined by medical history
- •Prematurity
- •Developmental delay isolated to motor delay.
- •Current gastroesophageal reflux
- •Current or history of liver or kidney disease
- •Severe irritability (as determined by the aberrant behavior checklist)
- •Drugs known to affect folate metabolism (e.g., methotrexate) and their derivatives
- •Patients who are receiving drugs that affect nitric oxide-mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil)
- •Patients who are receiving levodopa.
研究组 & 干预措施
Kuvan®
Patients will be instructed to take 20 mg/kg/day of Kuvan® orally dissolved in 4 - 8oz. of water or apple juice with breakfast.
干预措施: sapropterin dihydrochloride (Drug)
结局指标
主要结局
Preschool Language Scales
时间窗: 16 weeks
Change in the raw score from baseline of the Preschool Language Scales over the 16 week period. The raw score was measured at baseline, 8 weeks and 16 weeks after starting treatment and the change over the 16 week period from baseline to the end of the study was calculated. There was no imputed data and the analysis was as treated. The raw score ranged from 0 to 130. Higher scores indicate better performance.
次要结局
未报告次要终点
研究者
Richard Frye
Associate Professor of Pediatrics, Directory of Autism Research
Arkansas Children's Hospital Research Institute