Raloxifene for Women With Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborators:
Kaiser Permanente
Indiana University
Southern Illinois University
Information provided by (Responsible Party):
Victor W. Henderson, Stanford University
ClinicalTrials.gov Identifier:
NCT00368459
First received: August 22, 2006
Last updated: March 20, 2015
Last verified: March 2015
  Purpose

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


Condition Intervention Phase
Alzheimer Disease
Drug: raloxifene
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Raloxifene in Women With AD: Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-cog) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • Global Rating, Clinical Dementia Rating (CDR) Sum of Boxes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Global rating of dementia severity, change from baseline at 12 months. Range 0-5. For results below, positive change represents improvement/ better performance.

  • Function, Activities of Daily Living (ADL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • Behavior [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Neuropsychiatric Inventory, change from baseline at 12 months. Range 0-120. For results below, positive change represents improvement/ better performance.

  • Cognitive (Neuropsychological) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.

  • ADAS-cog [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change from baseline at 6 months, compared between groups. Error score range 0-70. For results below, positive change represents improvement/ better performance.

  • Clinical Dementia Rating, Sum of Boxes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change from baseline at 6 months, compared between groups. Range 0-5. For results below, positive change represents improvement/ better performance.

  • Function, Activities of Daily Living [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change from baseline at 6 months, compared between groups. Range 0-78. For results below, positive change represents improvement/ better performance.

  • Behavior [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Neuropsychiatric Inventory, change from baseline at 6 months, compared between groups. Range 0-120. For results below, positive change represents improvement/ better performance.

  • Cognition (Neuropsychological) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 42
Study Start Date: August 2006
Study Completion Date: January 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: raloxifene
oral raloxifene 120 mg once daily
Drug: raloxifene
Raloxifene is a selective estrogen receptor modulator
Other Name: Evista
Placebo Comparator: placebo
identical appearing oral placebo
Drug: Placebo
Identical appearing placebo
Other Name: There are no other names.

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).

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Exclusion Criteria:

1. Failure to meet inclusion criteria

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368459

Locations
United States, California
Kaiser Permanente Santa Rosa
Santa Rosa, California, United States, 95403
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Illinois
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Stanford University
Kaiser Permanente
Indiana University
Southern Illinois University
Investigators
Principal Investigator: Dr Victor Henderson Stanford University
  More Information

No publications provided

Responsible Party: Victor W. Henderson, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00368459     History of Changes
Other Study ID Numbers: IA0096
Study First Received: August 22, 2006
Results First Received: March 1, 2015
Last Updated: March 20, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
raloxifene, women

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Raloxifene
Bone Density Conservation Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on August 31, 2015