Raloxifene for Women With Alzheimer's Disease

Condition(s) targeted: Alzheimer's Disease

Intervention: raloxifene (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute on Aging (NIA)

Official(s) and/or principal investigator(s):
Victor Henderson, MD, Principal Investigator, Affiliation: Stanford University

Overall contact:
Narinder Bolaria, Phone: 650-721-3308, Email: nbolaria@stanford.edu

The purpose of this study is to determine whether Raloxifene, a selective estrogen receptor modulator (SERM), improves cognitive function in women with Alzheimer's disease.

Official title: Raloxifene in Women With AD: Randomized Controlled Trial

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Changes in cognitive subscale of the Alzheimer's Disease Assessment Scale

Secondary outcome:

Changes in Clinical Dementia Rating

Activities of Daily Living (Alzheimer's Disease Cooperative Study scale)

Neuropsychiatric Inventory

Cognitive subscale of the Alzheimer's Disease Assessment Scale

Other cognitive tests (East Boston Memory Test, Digit Ordering, category fluency, Trail Making Test, Boston Naming Test short version, Mini-Mental State examination, narrative writing, semantic binding)

Caregiver burden interview

Detailed description: Alzheimer's disease is the most common cause of dementia, and effective treatment options remain quite limited. Raloxifene, a selective estrogen receptor modulator (SERM), is approved at lower doses for treatment and prevention of osteoporosis in postmenopausal women. Its clinical profile is well known. In laboratory studies, this compound affects brain activity in ways that might be expected to improve cognitive function, and recent clinical data support the hypothesis that a higher dose of raloxifene could improve dementia symptoms in women with Alzheimer's disease.

This is a randomized, double-blind, placebo-controlled trial of raloxifene for the treatment of women with this disorder. Eligible women must have been on a stable effective dose of a cholinesterase inhibitor for at least six months prior to randomization. An estimated 72 women with mild to moderate dementia due to Alzheimer's disease will be enrolled at two sites in this pilot study, and treatment duration will be for 12 months.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Female, age 60+

- Postmenopausal

- Premorbid literacy and history of having been fluent in English

- Dementia present for at least 6 months beginning at age 60+

- Mild or moderate dementia (Mini-Mental State examination score 12-26, inclusive)

- Probable Alzheimer's disease

- Modified Ischemia Scale score of 4 or less

- Good physical health established by medical history, examination, and baseline

laboratory tests

- Effective dose of donepezil, rivastigmine, or galantamine for at least 6 months;

stable effective dose for at least 2 months

- Availability of a primary caregiver who knows the participant well and who is able to

accompany her for regular assessments during the course of the study

Exclusion Criteria:

- Concomitant neurological disorder likely to affect cognition

- Concomitant insulin-dependent diabetes or serious medical illness likely to limit the

ability to complete study protocol

- History of pulmonary embolism, deep vein thrombosis, or retinal vein occlusion

- Major depression within past year

- Experimental medication for the treatment of cognitive impairment associated with

dementia within 2 months

- Raloxifene within 6 months

- Systemic estrogen, progestin, or testosterone within 2 months

- Known contraindication to raloxifene

Narinder Bolaria, Phone: 650-721-3308, Email: nbolaria@stanford.edu

Kaiser Foundation Hospitals, Department of Neurology, Santa Rosa, California 95403, United States; Recruiting
Susan Kirk, RN, Phone: 707-571-3952, Email: Susan.Kirk@kp.org
Sue Stephenson, MD, Principal Investigator

Southern Illinois University, Springfield, Illinois 62794, United States; Recruiting
Barbara Lokaitis, Phone: 217-545-9737, Email: blokaitis@siumed.edu
Tom Ala, MD, Principal Investigator

Indianapolis University, Department of Neurology, Indianapolis, Indiana 46202-5111, United States; Recruiting
Sheryl Lynch, Phone: 317-278-8307, Email: slynch@iupui.edu
Julie Dickinson, Phone: 317-278-4333, Email: judickso@iupui.edu
Martin Farlow, MD, Principal Investigator

Related publications:

Yaffe K, Krueger K, Cummings SR, Blackwell T, Henderson VW, Sarkar S, Ensrud K, Grady D. Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial. Am J Psychiatry. 2005 Apr;162(4):683-90.

Starting date: August 2006
Ending date: July 2009
Last updated: October 14, 2008