{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:27:52Z","timestamp":1792787272654,"version":"4.5.0"},"reference-count":26,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"unspecified","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Novartis Pharmaceutical"},{"name":"University Hospital of Dijon Bourgogne"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,11,22]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3K\u03b1-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS). During its development, in patients with the MCAP subgroup of PROS, there was no specific, standardised evaluation of the effect on neuro-cognitive functioning. Moreover, it remains unknown if the molecule crosses the blood-brain barrier. Our objective is to evaluate the efficacy of a 24 month treatment with alpelisib on adaptive behaviour in patients with MCAP syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>SESAM is an industry-sponsored two-period multicentre French academic phase II trial, with a 6-month double-blind, placebo-controlled period followed by an open-label period. The primary endpoint is a \u22654-point improvement in the Vineland II Adaptive Behaviour Scale (VABS), 24 months after treatment initiation. Secondary objectives are safety, VABS improvement at 6 months, impact on the quality of life, epilepsy and hypotonia. 20 patients aged 2 to 40 years with an MCAP diagnosis and neurodevelopmental disorders of various degrees, will be followed monthly in local centres, centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. An optional lumbar puncture will be performed to investigate blood-brain barrier crossing. Inclusions were completed by April 2024, with the end of follow-up in November 2026.<\/jats:p>\n                    <jats:p>Given the efficacy of alpelisib in patients with PROS, if the drug crosses the blood-brain barrier, we can expect a clinical benefit for patients with neurocognitive disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was given by CPP Sud-Ouest et Outre-Mer I (reference: 2022-500197-34-01). Findings from this study will be disseminated via publication, reports and conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial\" xlink:href=\"NCT05577754\">NCT05577754<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-084614","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T20:44:56Z","timestamp":1734986696000},"page":"e084614","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["A phase II double-blind multicentre, placebo-controlled trial to assess the efficacy and safety of alpelisib (BYL719) in paediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP): the SESAM study protocol"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05577754","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04285723","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04980833","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04589650","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05577754","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-293X","authenticated-orcid":false,"given":"Maxime","family":"Luu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Vabres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Espitalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Garde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Racine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Carpentier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e9laide","family":"Rega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romaric","family":"Loffroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawale","family":"Hadouiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boddaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Curie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Guibaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Chebbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Charligny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-6303","authenticated-orcid":false,"given":"Paul","family":"Kuentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Canaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Bahi-Buisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Fleck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Cransac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-1837","authenticated-orcid":false,"given":"Marc","family":"Bardou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-444X","authenticated-orcid":false,"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"2024122102503344000_14.12.e084614.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2332"},{"key":"2024122102503344000_14.12.e084614.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2331"},{"key":"2024122102503344000_14.12.e084614.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.006"},{"key":"2024122102503344000_14.12.e084614.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds440"},{"key":"2024122102503344000_14.12.e084614.5","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.244"},{"key":"2024122102503344000_14.12.e084614.6","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.220"},{"key":"2024122102503344000_14.12.e084614.7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36552"},{"key":"2024122102503344000_14.12.e084614.8","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36836"},{"key":"2024122102503344000_14.12.e084614.9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31361"},{"key":"2024122102503344000_14.12.e084614.10","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/cge.13918","article-title":"Clinical 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