Effect of a Wide Spectrum Nutritional Supplement on Mitochondrial Function in Children With Autism Spectrum Disorder (ASD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Change in Mitochondrial Activity in Study Patients: Citrate Synthase
研究概览
简要总结
The objective of this study is to evaluate the metabolic effects of a comprehensive wide-spectrum supplement for children with ASD to determine whether it physiologically targets mitochondrial pathways known to be abnormal in children with ASD.The intervention is a commonly used wide-spectrum nutritional supplement, which is theoretically designed to normalize mitochondrial function. The investigators aim to determine if the supplement does have the hypothesized effect on physiology in individuals with ASD. The investigator will enroll up to 50 children, aged 4 to 14 years of age with confirmed ASD and mitochondrial dysfunction, and participation will last 26 weeks.
详细描述
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder often with life-long consequences that affects young children during critical developmental periods. The Centers for Disease Control estimates that ASD affects as many as 17 per 1000 children (1 in 59) in the United States suggesting that the prevalence is higher than previous estimates.Despite the dramatic rise in the detected prevalence of ASD over the past two decades, there is no effective medical treatment for core ASD symptoms (social communication and repetitive behavior), the closely associated problem of language impairment, or the underlying pathophysiology of ASD. Currently, the only accepted treatment for core ASD symptoms is behavior therapy, which may entail intensive one-on-one treatment over several years.
The primary aims of this study are to evaluate the effect of a wide-spectrum nutritional supplement on mitochondrial function in individuals with ASD. Participants entered into the trial will have abnormalities in mitochondrial function that are known to be associated with ASD (approximately 50+% of children with ASD) but are not diagnostic of mitochondrial disease. The investigators hypothesize that nutritional supplements designed for children with ASD have a physiological action of normalizing mitochondrial function and cellular physiology throughout the body.
To test whether the targeted nutritional supplement is superior to placebo, the investigators will study 50 children, between the ages of 4 years to 14 years, with confirmed ASD and known abnormal variations in mitochondrial at baseline. Participants will be randomly assigned to receive active treatment or placebo for 12-weeks under double-blind conditions and at the end of the 12 weeks switch to the opposite condition after *no wash out period. Mitochondrial function will be measured at baseline and after each treatment arm in order to determine if the supplement positively influences cellular biochemistry. The investigator will also evaluate the effectiveness of the supplement on core and associated ASD symptoms using several behaviors assessments.
*note: 2 week wash out period was eliminated from the design to prevent attrition before the study was started. The CT.gov record was not updated for this change in the protocol in a timely manner. Published paper reflects the no wash out period. CT record is being updated for clarity. .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight ≥ 15 kg and ≤ 100kg;
- •DSM-5 diagnosis of Autism Spectrum Disorder as established by formal clinical assessment which includes a gold-standard tool such as the Autism Diagnostic Observational Schedule.
- •Current Clinical Global Impression Severity score ≥ 4
- •Stable educational and therapy plan (one month) with no planned changes in the intensity of treatment for 12 weeks.
- •English is spoken in the home and at least one parent is able to read, write and speak English.
- •Stable medication (no changes in past 6 weeks and no planned changes for the study duration.
- •Electron Transport Chain Complex (I, II, III, IV) or Citrate Synthase Activity which is >= 2.0 Standard Deviation Above or Below Average (outside the normal range)
排除标准
- •Presence of serious behavioral problems (tantrums, aggression, self-injury) for which another treatment is warranted.
- •Current Clinical Global Impression Severity score < 7 (Extremely Ill)
- •Significant medical condition by history or by physical examination or lab tests that would be incompatible with the treatment.
- •Children taking anticonvulsant medication for seizures or active epilepsy.
- •Diagnosis of Mitochondrial Disease
研究组 & 干预措施
Wide-spectrum nutritional supplement
The Wide-spectrum nutritional supplement used will be a combination of NeuroNeeds: SpectrumNeeds and QNeeds. Weight based dosing will be used. The daily serving size will be divided into two oral daily doses in the form of a powder which can be mixed into liquid or food. Together, there are 34 different dietary supplements in the products. Except for ubiquinol, all of these nutrients are provided in a powder form in SpectrumNeeds. Ubiquinol is provided separately in QNeeds gel capsules. These capsules can be swallowed whole, or cut with scissors and the contents squeezed out and added to SpectrumNeeds just before ingestion.
干预措施: Wide-spectrum nutritional supplement (Drug)
Placebo control
Participants randomized to receive placebo will take placebo in an oral form divided into powder and a gel capsule in the same manner as treatment. For the second phase of the cross over, participants will be part of the opposite group they were assigned to in Phase I (Placebo or Treatment). Quantities for placebo or treatment will match across phases for each subject, utilizing the same weight based dosing.
干预措施: Placebo (Other)
结局指标
主要结局
Change in Mitochondrial Activity in Study Patients: Citrate Synthase
时间窗: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment. Normal Range 4.4 to 22 with Mean and SD of 12.1 and 5.1. It is better to be within the normal range than outside of the normal range regardless of whether the value is higher or lower.
Change in Mitochondrial Activity in Study Patients: Complex I
时间窗: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment. Normal range is 3.4 to 11.9 with a mean of 7.65. Outside of the normal range is worse regardless of whether it is above or below the normal range.
Change in Mitochondrial Activity in Study Patients: Complex II
时间窗: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment. Normal Range (mean ±SD) 0.03 -- 0.35 (0.194 ±0.08). It is better to be within the normal range regardless of whether the value is above or below the normal range
Change in Mitochondrial Activity in Study Patients: Complex IV
时间窗: Before (Baseline), After Part I (Week 12), After Part 2 (Week 24)
Mitochondrial activity and redox metabolism at baseline and after the placebo and supplement arms of the study, as determined through laboratory assessment. Normal Range (mean ±SD) 0.15 -- 0.6 (0.31 ±0.1). Better scores are inside the normal range regardless of if they are higher or lower.
次要结局
- Change in the Childhood Autism Rating Scale (CARS) Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Clinical Global Impression Scale (CGI) Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Children's Yale-Brown Obsessive Compulsive Scale Modified for Autism Spectrum Disorder (CYBOCS-ASD) Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Aberrant Behavior Checklist (ABC) Scores(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Parent-rated Anxiety Scale for ASD (PRAS-ASD) Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Caregiver Strain Questionnaire (CGSQ) Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Change in the Vineland III Caregiver Score(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
- Evaluate Intervention Safety(Screening, Baseline, After Week 4, After Week 8, After Week 12, Atter Week 16, After Week 20, After Week 24)
- Examine the Change in Cognitive Ability(Before (Baseline), After Part I (Week 12), After Part 2 (Week 24))
研究者
Richard Frye
Director of Research
Rossignol Medical Center