Phase II pilot randomized trial of zonisamide for disease modification in prodromal Lewy body disease.
Phase II pilot randomized trial of zonisamide for disease modification in prodromal Lewy body disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Nagoya, JP · Author affiliation
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.Location evidence
JP · Author affiliation · country only
Department of Neurology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.Location evidence
Fukushima, JP · Author affiliation
Drug Discovery and Cyclotron Research Center, Southern Tohoku Research Institute for Neuroscience, Fukushima, Japan.Location evidence
Tokyo, JP · Author affiliation
Affairs Department, Nihon Medi-Physics Co. Ltd., Tokyo, Japan.Location evidence
Takayama, JP · Author affiliation
Kumiai Kosei Hospital, Takayama, Gifu, Japan.Location evidence
Gifu, JP · Author affiliation
Kumiai Kosei Hospital, Takayama, Gifu, Japan.Location evidence
Kakegawa, JP · Author affiliation
Chutoen General Medical Center, Kakegawa, Shizuoka, Japan.Location evidence
Shizuoka, JP · Author affiliation
Chutoen General Medical Center, Kakegawa, Shizuoka, Japan.Location evidence
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Original abstract
Zonisamide exhibits potential neuroprotective properties, but its efficacy during the prodromal stage of Lewy body disease (LBD) remains unclear. In this phase II randomized, double-blind pilot trial, 29 high-risk individuals aged 50-80 years with ≥2 prodromal symptoms and abnormal DaT-SPECT and/or cardiac MIBG were randomized to zonisamide (50-100 mg/day, n = 14) or placebo (n = 15) and treated for 96 weeks. Participants with Parkinson's disease or dementia with Lewy bodies were excluded. No significant between-group difference was observed in the primary outcome, change in DaT-SPECT specific binding ratio from baseline to week 96 (0.072; 95% CI -0.565 to 0.709; p = 0.817), or in secondary outcomes including MIBG parameters and motor and cognitive functions. Non-motor symptoms worsened with zonisamide, whereas two placebo recipients developed Parkinson's disease. Somnolence, fatigue, decreased appetite, and constipation were frequent adverse events. Although findings are inconclusive due to limited power, this study provides valuable methodological insights for preventive LBD trials.