Raloxifene for Women With Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Raloxifene in Women With AD: Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00368459
• Other study ID #: IA0096
• Status: Completed
• Phase: Phase 2
• First received: August 22, 2006
• Last updated: March 20, 2015
• Start date: August 2006
• Est. completion date: January 2012

Study information

• Verified date: March 2015
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a multisite pilot randomized trial of raloxifene or placebo for the treatment of women with Alzheimer's disease.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: January 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

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

Exclusion Criteria:

1. Failure to meet inclusion criteria

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• raloxifene
Raloxifene is a selective estrogen receptor modulator
• Placebo
Identical appearing placebo

Locations

Country	Name	City	State
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Kaiser Permanente Santa Rosa	Santa Rosa	California
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Stanford University School of Medicine	Stanford	California

Sponsors (4)

Lead Sponsor	Collaborator
Stanford University	Indiana University, Kaiser Permanente, Southern Illinois University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months	No
Secondary	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.	12 months	No
Secondary	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.	12 months	No
Secondary	Behavior	Neuropsychiatric Inventory, change from baseline at 12 months. Range 0-120. For results below, positive change represents improvement/ better performance.	12 months	No
Secondary	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.	12 months	No
Secondary	ADAS-cog	Change from baseline at 6 months, compared between groups. Error score range 0-70. For results below, positive change represents improvement/ better performance.	6 months	No
Secondary	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.	6 months	No
Secondary	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.	6 months	No
Secondary	Behavior	Neuropsychiatric Inventory, change from baseline at 6 months, compared between groups. Range 0-120. For results below, positive change represents improvement/ better performance.	6 months	No
Secondary	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.	6 months	No