This is a multisite pilot randomized trial of raloxifene or placebo for the treatment of women with Alzheimer's disease.
Raloxifene , a selective estrogen receptor modulator, has attracted attention as a potential treatment for Alzheimer's disease in women, but it has not been studied in this disorder. To assess feasibility of large-scale efficacy trials and to obtain an initial estimate of treatment effect, study investigators plan to conduct a pilot, randomized, double blind, placebo-controlled, clinical trial of high-dose (120 mg daily) raloxifene. Eligible participants are postmenopausal women with late-onset Alzheimer's disease of mild-to-moderate severity taking a stable dose of an approved cholinesterase inhibitor. This pilot study is not designed to have power to detect significant, modest between-group differences of the magnitude provided by current FDA-approved therapies. Study participants will be randomly allocated to oral raloxifene or identical placebo over a 12 month period. Outcomes of interest will be obtained at 6 and 12 months. The prespecified primary outcome is the change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog), compared between groups at 12 months. Prespecified secondary outcomes include measures of global severity (Clinical Dementia Rating sum of boxes), function (Activities of Daily Living), behavior (Neuropsychiatric inventory), and other neuropsychological measures. Caregiver outcomes will be burden (Zarit burden inventory) and distress (from the Neuropsychiatric inventory).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
Raloxifene is a selective estrogen receptor modulator
Identical appearing placebo
Kaiser Permanente Santa Rosa
Santa Rosa, California, United States
Stanford University School of Medicine
Stanford, California, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-cog)
ADAS-cog, change from baseline at 12 months, compared between treatment arms. The ADAS-cog is a neuropsychological battery commonly used in trials of AD patients. Error score range 0-70. For results below, positive change represents improvement/ better performance. For the primary outcome, as well as for secondary outcomes, the reported p-values reflect the calculated p-values.
Time frame: 12 months
Global Rating, Clinical Dementia Rating (CDR) Sum of Boxes
Global rating of dementia severity, change from baseline at 12 months. Range 0-5. For results below, positive change represents improvement/ better performance.
Time frame: 12 months
Function, Activities of Daily Living (ADL)
ADL scale from the Alzheimer's Disease Cooperative Study, change from baseline at 12 months. Range 0-78. For results below, positive change represents improvement/ better performance.
Time frame: 12 months
Behavior
Neuropsychiatric Inventory, change from baseline at 12 months. Range 0-120. For results below, positive change represents improvement/ better performance.
Time frame: 12 months
Cognitive (Neuropsychological)
Global composite calculated as a weighted average of standardized scores of neuropsychological tests (weighted by the inverse intertest correlation matrix), change from baseline at 12 months. There is no theoretical maximum or minimum for this cognitive composite, with a score of 0 standardized units representing no change. For results below, positive change represents improvement/ better performance.
Time frame: 12 months
ADAS-cog
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Change from baseline at 6 months, compared between groups. Error score range 0-70. For results below, positive change represents improvement/ better performance.
Time frame: 6 months
Clinical Dementia Rating, Sum of Boxes
Change from baseline at 6 months, compared between groups. Range 0-5. For results below, positive change represents improvement/ better performance.
Time frame: 6 months
Function, Activities of Daily Living
Change from baseline at 6 months, compared between groups. Range 0-78. For results below, positive change represents improvement/ better performance.
Time frame: 6 months
Behavior
Neuropsychiatric Inventory, change from baseline at 6 months, compared between groups. Range 0-120. For results below, positive change represents improvement/ better performance.
Time frame: 6 months
Cognition (Neuropsychological)
Global composite calculated as a weighted average of standardized scores of neuropsychological tests (weighted by the inverse intertest correlation matrix), change from baseline at 6 months. There is no theoretical maximum or minimum for this cognitive composite, with a score of 0 standardized units representing no change. For results below, positive change represents improvement/ better performance.
Time frame: 6 months