Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3–12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen’s d 0.21; 95% CI − 0.46, 0.88 and 0.10; 95% CI − 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen’s d − 0.96; 95% CI − 1.73, − 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell. The sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase. SF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers’ assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures. Trial registration: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense.

中文翻译：

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自闭症谱系障碍儿童萝卜硫素及其代谢物发现的随机对照试验

萝卜硫素 (SF) 是西兰花中的一种异硫氰酸酯，通过其对多种代谢和免疫途径的影响，具有与自闭症谱系障碍 (ASD) 相关的潜在益处。先前的口服 SF 临床试验证明了对年轻男性行为和 ASD 儿童尿液代谢组学变化的积极临床影响。我们对 57 名年龄在 3-12 岁、ASD 超过 36 周的儿童进行了为期 15 周的随机平行双盲安慰剂对照临床试验，其中包括 15 周的开放标签治疗和 6 周的无治疗延长期。28 人被分配 SF，29 人接受安慰剂 (PL)。测量 SF 的临床效果、安全性和耐受性以及生物标志物，以阐明 SF 在 ASD 中的作用机制。分析了 22 名服用 SF 和 23 名服用 PL 的儿童的数据。治疗对主要结果测量的影响，俄亥俄州自闭症临床印象量表 (OACIS) 在 7 周和 15 周时，SF 和 PL 组的自闭症总体水平不显着。对 OACIS 的影响大小无统计学意义但为正，表明接受 SF 治疗的患者可能有更大改善的趋势（Cohen's d 0.21；95% CI - 0.46、0.88 和 0.10；95% CI - 0.52、0.72、分别）。在开放标签阶段使用 SF 时，两组在所有分量表上都有所改善。在 15 周时，护理人员对次要结果测量的评分在异常行为检查表 (ABC) 上显着提高 (Cohen's d − 0.96; 95% CI − 1.73, − 0.15)，但在社会反应量表 2 (SRS-2) 上没有。与治疗前基线相比，对 SF 暴露时间的非随机分析提高了 ABC 和 SRS-2 的评分（p < 0.001）。与 PL 相比，SF 在谷胱甘肽氧化还原状态、线粒体呼吸、炎症标志物和热休克蛋白的生物标志物方面有显着变化。临床实验室研究证实了产品的安全性。SF 的耐受性非常好，治疗的副作用不严重，包括罕见的失眠、烦躁和对味觉和嗅觉的不耐受。样本量仅限于 45 名患有 ASD 的儿童，我们没有估算缺失数据。与 PL 相比，我们无法记录 SF 与 PL 患者在临床就诊期间临床评估的显着变化。在开放标签阶段，安慰剂效应混淆了临床结果。SF 导致主要结果测量的总分和所有子量表得分发生微小但无统计学意义的变化，而对于次要结果测量，照顾者对服用 SF 的儿童的评估显示，与那些在 ABC 上服用 PL 而不是 SRS-2 的儿童相比，有统计学意义的改善。与我们之前对患有 ASD 的年轻男性进行的富含 SF 制剂的试验相比，SF 在儿童中的临床效果不太明显。SF 对生物标志物的一些影响与临床改善相关。根据我们的二级临床措施，SF 的耐受性非常好，安全有效。试验注册：本研究于 2015 年 9 月 28 日在临床试验网站 (clinicaltrials.gov) (NCT02561481) 进行了前瞻性注册。资金由美国国防部提供。与我们之前对患有 ASD 的年轻男性进行的富含 SF 制剂的试验相比，SF 在儿童中的临床效果不太明显。SF 对生物标志物的一些影响与临床改善相关。根据我们的二级临床措施，SF 的耐受性非常好，安全有效。试验注册：本研究于 2015 年 9 月 28 日在临床试验网站 (clinicaltrials.gov) (NCT02561481) 进行了前瞻性注册。资金由美国国防部提供。与我们之前对患有 ASD 的年轻男性进行的富含 SF 制剂的试验相比，SF 在儿童中的临床效果不太明显。SF 对生物标志物的一些影响与临床改善相关。根据我们的二级临床措施，SF 的耐受性非常好，安全有效。试验注册：本研究于 2015 年 9 月 28 日在临床试验网站 (clinicaltrials.gov) (NCT02561481) 进行了前瞻性注册。资金由美国国防部提供。