Alzheimer's Disease: Therapeutic Potential of Estrogen

Study Overview
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Brief Summary
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This is a 15-month study to determine the effectiveness of hormone replacement therapy in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease.

Detailed Description
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Estrogen is a naturally occurring hormone produced in a woman's body. The purpose of this 15-month study is to determine the effectiveness of hormone replacement therapy in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease and without other dementias. Patients who volunteer for this study will either receive a patch containing 17-ß-estradiol or will receive an inactive placebo patch. In addition, patients will be given either medroxyprogesterone or an inactive placebo pill. Neither the volunteers nor the study staff will know which type of patch or pill a patient receives. Patients must be generally healthy and have mild-to-moderate dementia. There must be a patient caregiver who can watch for side effects and ensure that the patient takes the study medications on schedule. Patients will undergo neuropsychological tests and an evaluation of the ability to live independently at each visit as well as laboratory evaluations, such as the taking of blood. Each visit will last approximately 3 hours. A total of 160 participants are being recruited.

Official Title
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Alzheimer's Disease: Therapeutic Potential of Estrogen

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Transdermal estradiol
* Drug: Medroxyprogesterone
* Drug: Placebo Patch
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women with Alzheimer's disease and without other dementias (diagnosed by study staff or from an outside clinic) Mini Mental State Examination score greater than 15/30 Exclusion Criteria: History of cancer of reproductive tissues History of deep vein thrombosis or blot clots Diabetes Heart disease or stroke Liver problems including hepatitis Severe vision or hearing problems Tobacco use Lack of an adequate caregiver inability to perform psychometric testing

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>estradiol patch and medroxyprogesterone | Drug: Transdermal estradiol<br>* 50 micrograms (low-dose) or 100 micrograms (high-dose) transdermal 17-ß-estradiol patch, changed every 3 days, for 12 months<br>* Other names: Estrogen replacement therapy;Drug: Medroxyprogesterone<br>* 2.5mg tablet daily for 12 months<br>* Other names: progesterone;|
| Active Comparator: 2<br>estradiol patch and placebo pill | Drug: Transdermal estradiol<br>* 50 micrograms (low-dose) or 100 micrograms (high-dose) transdermal 17-ß-estradiol patch, changed every 3 days, for 12 months<br>* Other names: Estrogen replacement therapy;Drug: Placebo<br>* Placebo tablet daily for 12 months<br>|
| Active Comparator: 3<br>placebo patch and medroxyprogesterone | Drug: Medroxyprogesterone<br>* 2.5mg tablet daily for 12 months<br>* Other names: progesterone;Drug: Placebo Patch<br>* Transdermal placebo patch, changed every 3 days, for 12 months<br>|
| Placebo Comparator: 4<br>placebo patch and placebo pill | Drug: Placebo Patch<br>* Transdermal placebo patch, changed every 3 days, for 12 months<br>Drug: Placebo<br>* Placebo tablet daily for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition: delayed recall on Buschke Selective Reminding Test; Stroop Interference condition--completion time and errors; Clinician-rated Interview Based Impression of Change |  | Baseline and 1, 3, 6, 12, and 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skills of Independent Living: Physical functioning Performance (PFP) |  | Baseline and 1, 3, 6, 12, and 15 months | 
| Bioassays (Estradiol, estrone, medroxyprogesterone, FSH, influence of ApoE genotype in responsivity to estrogen) |  | Baseline and 1, 3, 6, 12, and 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer disease, Hormone replacement therapy, Postmenopausal women