Background <p>Spasticity is a hallmark of hereditary spastic paraplegia (HSP) and contributes to gait impairment. <i>Alpinia zerumbet</i> oil (Ziclague^®) is a topical anti-spastic agent approved in Brazil, but not yet explored in HSP. Then, it was designed a randomized, placebo-controlled, double-blind, crossover trial to evaluate the efficacy and safety of Ziclague^® in patients with HSP: the ZISPAST trial.</p> Methods <p>Each participant was randomly assigned to receive 0.8 mL of Ziclague^® dermal applications (0.064 mL of <i>Alpinia Zerumbet</i> 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.</p> Results <p>Fifty-seven patients were enrolled, 37 (64.9%) of whom were men and 50 (87.7%) with pure phenotype. Mean age was 44 (± 11.6; range, 22 to 74), mean age of onset 23 (± 16.6; range, &lt; 1 to 62) and mean disease duration 21 (± 13.1; 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 (<i>p</i> = 0.56).</p> Conclusions <p>Ziclague^® was safe in patients with HSP, but it was not able to improve gait velocity considering methods and protocol used.</p> Trial registration number <p>U1111-1218-2539. Registered 28 August 2018, <a href="https://ensaiosclinicos.gov.br/rg/RBR-83xh37">https://ensaiosclinicos.gov.br/rg/RBR-83xh37</a>.</p>