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

Yuan Dai¹, Lingli Zhang¹, Juehua Yu², Xin Zhou³, Hua He¹, Yiting Ji¹, Kai Wang¹, Xiujuan Du¹, Xin Liu¹, Yun Tang⁴, Shining Deng¹, Christelle Langley⁵, Wei-Guang Li⁶, Jun Zhang¹, Jianfeng Feng⁷, Barbara J Sahakian⁸, Qiang Luo⁹, Fei Li¹⁰

Affiliations

¹ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
² Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
³ Clinical Research Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
⁴ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; The School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China.
⁵ Department of Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB21TN, UK.
⁶ Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁷ Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China.
⁸ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB21TN, UK; Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China.
⁹ Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China; State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: qluo@fudan.edu.cn.
¹⁰ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: feili@shsmu.edu.cn.

PMID: 36654288
DOI: 10.1016/j.scib.2021.01.008

Free article

Randomized Controlled Trial

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

Yuan Dai et al. Sci Bull (Beijing). 2021.

Free article

. 2021 Aug 15;66(15):1591-1598.

doi: 10.1016/j.scib.2021.01.008. Epub 2021 Jan 16.

Authors

Affiliations

¹ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
² Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Centre for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
³ Clinical Research Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
⁴ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; The School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China.
⁵ Department of Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB21TN, UK.
⁶ Collaborative Innovation Center for Brain Science, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁷ Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China.
⁸ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Department of Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB21TN, UK; Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China.
⁹ Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai 200433, China; State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: qluo@fudan.edu.cn.
¹⁰ Department of Developmental and Behavioural Pediatric & Child Primary Care, Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: feili@shsmu.edu.cn.

PMID: 36654288
DOI: 10.1016/j.scib.2021.01.008

Abstract

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 and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD. However, the clinical significance remains uncertain, and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.

Keywords: Autism spectrum disorder; Bumetanide; Children; GABA; RCT.

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Conflict of interest The authors declare that they have no conflict of interest.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials