{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:26:27Z","timestamp":1791293187864,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T00:00:00Z","timestamp":1514332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"French Ministry of Health (National PHRC)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rett Syndrome (<jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2\u2010deficient mice, a model of <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The trial was a 6\u2010month, multicenter, randomized, double\u2010blind, placebo\u2010controlled study registered with ClinicalTrials.gov, number <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2\u20133\u00a0mg\/kg Desipramine per day (high Desipramine), 1\u20132\u00a0mg\/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (<jats:styled-content style=\"fixed-case\">AHI<\/jats:styled-content>), defined by the number of apnea and hypopnea events per hour, assessed at 6\u00a0months from baseline. Intention\u2010to\u2010treat analysis was applied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median change in <jats:styled-content style=\"fixed-case\">AHI<\/jats:styled-content> from baseline to 6\u00a0months was \u221231 (IQR: \u221237 to \u221211) for the high Desipramine, \u221217.5 (IQR: \u221231 to 13) for the low Desipramine, and \u221213 (IQR:\u221231 to 0) for the placebo group. We did not find any significant difference in these changes between the groups (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.781). A significant inverse correlation between Desipramine plasma concentration and <jats:styled-content style=\"fixed-case\">AHI<\/jats:styled-content> (<jats:italic>r\u00a0<\/jats:italic>=\u00a0\u22120.44; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0002) was underlined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This first clinical trial of desipramine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of <jats:styled-content style=\"fixed-case\">AHI<\/jats:styled-content> provided additional and relevant reasons to test the noradrenergic pathway in <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.468","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T05:13:00Z","timestamp":1514351580000},"page":"118-127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effect of desipramine on patients with breathing disorders in <scp>RETT<\/scp> syndrome"],"prefix":"10.1002","volume":"5","author":[{"given":"Josette","family":"Mancini","sequence":"first","affiliation":[{"name":"Neuropediatric Unit Aix Marseille University Children Hospital APHM, Timone, Neurosciences Institute Marseille 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