A comparative trial of selegiline and zonisamide for disease modifying effects on DAT-SPECT in patients with Parkinson’s disease: study protocol for a prospective multicenter randomized study (DATSZ-PD study)

Abstract Background: Therapeutic strategies to prevent degeneration of dopaminergic neurons in Parkinson’s disease have not been developed to date. Although previous non-clinical and clinical studies have shown that selegiline and zonisamide can protect dopamine neurons, their protective action has been clinically evaluated in few studies. In this study, we will compare levodopa/decarboxylase inhibitor (DCI) alone with the combination of levodopa/DCI and selegiline or zonisamide to investigate whether degeneration of dopaminergic neurons could be prevented by the combination therapy in patients with early Parkinson’s disease. Methods: This multicenter, open-label, randomized controlled study will enroll 180 patients. Sixty patients will be randomly assigned to receive levodopa/DCI alone, 60 patients will be assigned to receive levodopa/DCI and selegiline, and 60 patients will be assigned to receive levodopa/DCI and zonisamide, and followed-up for 1 year. The primary endpoint is the percent change of specific binding ratio (SBR; Southampton’s method) of 123Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT) (dopamine transporter SPECT, DAT-SPECT) from baseline to the end of one-year follow-up. The secondary endpoints are the percent change of Unified Parkinson’s Disease Rating Scale (Part II and Part III) scores and Parkinson's Disease Questionnaire -39 scores from baseline to post-treatment. Discussion: This multicenter, randomized controlled study will evaluate the disease-modifying effect of selegiline and zonisamide on degeneration of nigrostriatal dopaminergic neurons in patients with Parkinson’s disease based on the percent change of SBR of DAT-SPECT (primary endpoint). If our study findings suggest that selegiline or zonisamide has a disease-modifying effect from the clinical aspect, the long-term efficacy should be evaluated in a larger-scale phase III study. T Trial Registration: University hospital medical information network (UMIN): UMIN000022533. Registered 30 May 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025960