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Then, it was designed a randomized, placebo-controlled, double-blind, crossover trial to evaluate the efficacy and safety of Ziclague<jats:sup>\u00ae<\/jats:sup> in patients with HSP: the ZISPAST trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Each participant was randomly assigned to receive 0.8 mL of Ziclague<jats:sup>\u00ae<\/jats:sup> dermal applications (0.064 mL of <jats:italic>Alpinia Zerumbet<\/jats:italic> equally divided in each adductor magnus and each triceps surae) or placebo 0.9%. The primary endpoint was change from baseline in self-selected gait velocity and secondary endpoints included changes in maximal gait velocity, walking endurance, spasticity, muscle strength, Spastic Paraplegia Rating Scale, pain, fatigue, quality of life and post-treatment perceived change and general impression. Adverse events (AE) were also recorded.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Fifty-seven patients were enrolled, 37 (64.9%) of whom were men and 50 (87.7%) with pure phenotype. Mean age was 44 (\u00b1\u200911.6; range, 22 to 74), mean age of onset 23 (\u00b1\u200916.6; range, &lt; 1 to 62) and mean disease duration 21 (\u00b1\u200913.1; range, 2 to 54) years. Compared to baseline, there were no significant between-group differences in primary and secondary outcomes. There were few AEs, all of them mild. Incidence of AE was similar between treatment arms (<jats:italic>p<\/jats:italic>\u2009=\u20090.56).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Ziclague<jats:sup>\u00ae<\/jats:sup> was safe in patients with HSP, but it was not able to improve gait velocity considering methods and protocol used.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration number<\/jats:title>\n            <jats:p>U1111-1218-2539. Registered 28 August 2018, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/ensaiosclinicos.gov.br\/rg\/RBR-83xh37\" ext-link-type=\"uri\">https:\/\/ensaiosclinicos.gov.br\/rg\/RBR-83xh37<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-04007-5","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:53:39Z","timestamp":1758736419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ziclague\u00ae (Alpinia Zerumbet oil) in patients with hereditary spastic paraplegia - the randomized controlled ZISPAST trial"],"prefix":"10.1186","volume":"20","author":[{"given":"Fabricio Diniz","family":"de Lima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiane Raisa","family":"Servelhere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda Ribeiro","family":"Bittar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carelis","family":"Gonz\u00e1lez-Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Rolim Muro","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Benaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benilton","family":"de S\u00e1 Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luiz","family":"Pedroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando","family":"Graziani Povoas Barsottini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamarli","family":"Nucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcondes Cavalcante","family":"Fran\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"issue":"4","key":"4007_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/ana.24611","volume":"79","author":"R Sch\u00fcle","year":"2016","unstructured":"Sch\u00fcle R, Wiethoff S, Martus P, et al. 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