RATIONALE AND DESIGN OF A MULTICENTER STUDY OF SELEGILINE AND ALPHA-TOCOPHEROL IN THE TREATMENT OF ALZHEIMER-DISEASE USING NOVEL CLINICAL OUTCOMES

This report describes the rationale and design of a clinical trial usi ng selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the progression of dementia in Alzheimer disease (AD). This study was developed by the Alzheimer's Disease Cooperative Study (ADCS), a conso rtium of clinical research centers actively involved in AD research. T he major goal of the consortium is to design and conduct clinical inve stigations leading to the development of treatments for AD. This study uses a randomized double-blind, placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for the treatment of AD. The p rimary outcome of the study is the time to reach any one of the follow ing four endpoints: death, institutionalization, loss of two of three basic activities of daily living, and progression of Clinical Dementia Rating (CDR) stage from 2 to 3. Patients with moderately severe disea se (CDR=2) were enrolled and evaluated 10 times over a period of 2 yea rs to determine if these agents reduce the time to reach any endpoint. A database from the Consortium to Establish a Registry for Alzheimer' s Disease indicated adequate power analyses to observe a treatment eff ect on this clinically meaningful outcome measure. Recruitment and bas eline characteristics of the population are provided. The rationale fo r the choice of a factorial design, the use of a novel, clinically mea ningful endpoint, and the selection of a cohort of patients with AD of moderate severity are discussed.