本邦に於ける治療介入を伴う臨床研究を実施する上での問題点：DASH–PD研究の経験から

抄録

Introduction : Parkinson's disease–associated dementia (PDD) greatly contribute to the poor prognosis of Parkinson's disease. Although cholinesterase inhibitors including donepezil are effective for the treatment of PDD, the average life–expectancy of patients who developed PDD remains considerably short. An early therapeutic intervention that can prevent the onset of PDD may enable to improve the long–term prognosis of Parkinson's disease substantially. Our previous study showed that olfactory dysfunction could be a predictive indicator of the development of PDD. In this trial, we investigated whether early administration of donepezil to patients with severe olfactory dysfunction can reduce risk for the subsequent development of PDD.

This is a multi–center, randomised, double–blind, parallel group, placebo–controlled trial in patients with Parkinson's disease, who have severe hyposmia and who have not yet developed PDD. 200 patients will be randomly allocated in a 1:1 ratio either to receive donepezil or placebo, in addition to standard therapy for Parkinson's disease. Patients will be followed up every 6 months until the onset of PDD or for a maximum of 4 years (208 weeks). Primary endpoint is the onset of PDD, which is measured by the Mini–Mental State Examination and the Clinical Dementia Rating (CDR) stage. Secondary endpoint is cognitive impairment, which is measured by the Addenbrooke's Cognitive Examination–Revised score and the CDR stage. Statistical analysis will be made to evaluate whether donepezil has a favorable effect on the risk of developing PDD. The study was approved by the ethics committees of Tohoku University Graduate School of Medicine and the National Hospital Organization, Sendai–Nishitaga Hospital and registered at UMIN Clinical Trials Registry (UMIN000009958).