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In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3\u201311 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose\/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2\u201318 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0\u2009mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (<jats:italic>P<\/jats:italic>: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (<jats:italic>P<\/jats:italic>: 0.0043) and the SRS score by more than 10 points (<jats:italic>P<\/jats:italic>: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0\u2009mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit\/risk ratio particularly at 1.0\u2009mg twice daily.<\/jats:p>","DOI":"10.1038\/tp.2017.10","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T14:42:05Z","timestamp":1489502525000},"page":"e1056-e1056","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":161,"title":["Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders"],"prefix":"10.1038","volume":"7","author":[{"given":"E","family":"Lemonnier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Villeneuve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sonie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Serret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Rosier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Roue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Brosset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Viellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Bernoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Rondeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Thummler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ravel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Ben-Ari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"BFtp201710_CR1","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.neuroscience.2014.08.001","volume":"279C","author":"Y Ben-Ari","year":"2014","unstructured":"Ben-Ari Y . 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EL, DR and YB-A are founders and shareholders of the company. The remaining authors declare no conflicts of interest. Funding of the trial comes from an investment of Symmetry Capital, a grant from France's Agence Nationale de la Recherche (ANR-12-RPIB-0001-01) and French Government loans. We are grateful to the Bettencourt-Schuller foundation for support of the experimental investigations on ASD.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}