Raloxifene for Women With Alzheimer's Disease

NCT ID: NCT00368459

Last Updated: 2015-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2012-01-31

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).

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

raloxifene

oral raloxifene 120 mg once daily

Group Type: EXPERIMENTAL

raloxifene

Intervention Type: DRUG

Raloxifene is a selective estrogen receptor modulator

placebo

identical appearing oral placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical appearing placebo

Interventions

raloxifene

Raloxifene is a selective estrogen receptor modulator

Intervention Type: DRUG

Placebo

Identical appearing placebo

Intervention Type: DRUG

Other Intervention Names

Evista; There are no other names.

Eligibility Criteria

Inclusion Criteria

1. Female

2. Post menopausal

3. Age at least 60 years

4. Eight or more years of education with a history of premorbid literacy

5. By history, fluent speaker of English

6. Dementia (DSM-IV-derived criteria) present for at least six months beginning at age 60 or older

7. Mild or moderate dementia, defined by Mini-Mental State examination (MMSE) score between 12 and 26, inclusive

8. 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

9. Neurological history and examination within normal limits for age, except for changes consistent with AD or age

10. Modified Ischemia Scale score of 4 or less

11. Good physical health established by medical history, physical exam, and baseline laboratory tests

12. Blood pressure < 180/100 at time of entry

13. No history of, or examination evidence for, current insulin-dependent diabetes, stroke thought to impair cognition (e.g., cortical or thalamic infarct), or other focal brain lesion or neurological disorder likely to affect cognition, or other serious medical illness likely to limit participant's ability to complete study protocol

14. No history of pulmonary embolism, deep vein thrombosis, or retinal vein occlusion

15. No Diagnostic and Statistical Manual (DSM) IV criteria for Major Depressive Episode or other Axis I psychiatric disorder, other than AD, within the past year

16. Effective dose of an FDA-approved cholinesterase inhibitor for at least 6 months prior to randomization (usually donepezil 5 or 10 mg/d, rivastigmine 6 to 12 mg/d, or galantamine 16 to 24 mg/d); stable effective dose for at least 2 months prior to randomization

17. No psychotropic medication within 4 weeks of study entry or stable dose (for at least 4 weeks month) of psychotropic medications

18. No experimental mediation for the treatment of cognitive impairment associated with dementia within 2 months of study entry

19. No raloxifene within 6 months of study entry

20. No systemic estrogen, progestin, testosterone, related gonadal hormone therapy within 2 months of study entry

21. No other known contraindication to raloxifene or donepezil

22. A primary caregiver who knows the participant well and who is able to accompany her for regular assessments during the course of the study

23. Assent or consent of participant plus informed consent from participant's next of kin or legally authorized representative

• Minimum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Kaiser Permanente

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: collaborator

Southern Illinois University

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Victor W. Henderson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr Victor Henderson

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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

Countries

United States

Other Identifiers

IA0096

Identifier Type: -

Identifier Source: org_study_id