Improved symptoms following bumetanide treatment in children aged 3−6 years with autism spectrum disorder: a randomized, double-blind, placebo-controlled trial

作者：Yuan Dai, Lingli Zhang, Juehua Yu, Xin Zhou, Hua He, Yiting Ji, Kai Wang, Xiujuan Du, Xin Liu, Yun Tang, Shining Deng, Christelle Langley, Wei‐Guang Li, Jun Zhang, Jianfeng Feng, Barbara J. Sahakian, Qiang Luo, Fēi Li · 发表于：中国科学通报：英文版 · 年份：2021 · DOI：10.1016/j.scib.2021.01.008 · 被引用次数：42 · 研究领域：Autism Spectrum Disorder Research、Genetics and Neurodevelopmental Disorders、Neuroscience and Neural Engineering

With the current limited drug therapy for the core symptoms of autism spectrum disorder (ASD), we herein report a randomized, double-blind, placebo-controlled trial to investigate the efficacy, safety, and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old. A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo. In the final sample, 119 children received at least one dose of bumetanide (59 children) or placebo (60 children) were included in the final analysis. The primary outcome was a reduction in the Childhood Autism Rating Scale (CARS) score, and the secondary outcomes were the Clinical Global Impressions Scale (CGI) -Global Improvement (CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule (ADOS). Magnetic resonance spectroscopy (MRS) was used to measure γ-aminobutyric acid (GABA) and glutamate neurotransmitter concentrations in the insular cortex (IC) before and after the treatment. As compared with the placebo, bumetanide treatment was significantly better in reducing the severity. No patient withdrew from the trial due to adverse events. The superiority of bumetanide to placebo in reducing insular GABA, measured using MRS, was demonstrated. The clinical improvement was associated with a decrease in insular GABA in the bumetanide group. In conclusion, this trial in a large group of young children with predominantly moderate an...