Alzheimer's disease (AD) is the most common cause of dementia, and effective treatment options are distressingly limited. Raloxifene, a selective estrogen receptor modulator (SERM), is approved for treatment and prevention of osteoporosis in postmenopausal women. Its clinical profile is well known, and drug side-effects are generally well tolerated. In animal studies, this compound affects neural activity in ways that might be expected to improve cognitive function, and recent clinical data support the hypothesis that raloxifene could ameliorate dementia symptoms in women with AD. Over a three-year period of time, we will undertake a parallel-groups, randomized, double-blind, placebo-controlled pilot trial of raloxifene for the treatment of women with AD. Eligible participants must have been on an effective dose of a cholinesterase inhibitor (donepezil) for at least six months prior to randomization. A total of 72 women with mild to moderate dementia due to AD will be enrolled in this pilot study, and treatment duration will be for 12 months. Studies will be conducted at two performance sites, the University of Arkansas for Medical Sciences and Indiana University. Our first specific aim is to assess effect sizes of raloxifene on study outcomes as a guide to future clinical trials with this agent for women with AD.
Our second aim i s to determine if raloxifene compared to placebo substantially improves cognitive function and other specified outcomes. The hallmark of AD is cognitive deterioration, and our primary outcome instrument is the cognitive subscale of the Alzheimer's Disease Assessment Scale. Secondary outcomes are global change, function in activities of daily living, behavior, measures of specific cognitive skills, caregiver burden, and select biomarkers. The primary outcome will be assessed at three, six, nine, and 12 months. Primary analyses will be based on the month 12 assessment using an intention to treat analysis. It is anticipated that findings from this pilot study will provide useful guidance to plan and conduct future studies of raloxifene in women with mild to moderate symptoms of dementia due to AD.
Showing the most recent 10 out of 12 publications
