Raloxifene in Women With AD: Randomized Controlled Trial
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Stanford University
- Enrollment
- 42
- Locations
- 4
- Primary Endpoint
- Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-cog)
Overview
Brief Summary
This is a multisite pilot randomized trial of raloxifene or placebo for the treatment of women with Alzheimer's disease.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Post menopausal
- •Age at least 60 years
- •Eight or more years of education with a history of premorbid literacy
- •By history, fluent speaker of English
- •Dementia (DSM-IV-derived criteria) present for at least six months beginning at age 60 or older
- •Mild or moderate dementia, defined by Mini-Mental State examination (MMSE) score between 12 and 26, inclusive
- •National Institute of Neurological and Communicative Disease and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable Alzheimer's disease (AD) based on results of a neurologist's evaluation and laboratory tests
- •Neurological history and examination within normal limits for age, except for changes consistent with AD or age
- •Modified Ischemia Scale score of 4 or less
- •Good physical health established by medical history, physical exam, and baseline laboratory tests
Exclusion Criteria
- •Failure to meet inclusion criteria
Arms & Interventions
raloxifene
oral raloxifene 120 mg once daily
Intervention: raloxifene (Drug)
placebo
identical appearing oral placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-cog)
Time Frame: 12 months
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.
Secondary Outcomes
- Function, Activities of Daily Living (ADL)(12 months)
- Behavior(6 months)
- Cognitive (Neuropsychological)(12 months)
- Function, Activities of Daily Living(6 months)
- Global Rating, Clinical Dementia Rating (CDR) Sum of Boxes(12 months)
- ADAS-cog(6 months)
- Cognition (Neuropsychological)(6 months)
- Clinical Dementia Rating, Sum of Boxes(6 months)
Investigators
Victor W. Henderson
Professor
Stanford University