Alzheimer's Disease: Therapeutic Potential of Estrogen

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Transdermal estradiol; Drug: Medroxyprogesterone; Drug: Placebo; Drug: Placebo Patch

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Memory Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Sanjay Asthana, MD, University of Wisconsin - Madison, William S. Middleton VA Hospital

Publications and helpful links

General Publications

• Cholerton B, Gleason CE, Baker LD, Asthana S. Estrogen and Alzheimer's disease: the story so far. Drugs Aging. 2002;19(6):405-27. doi: 10.2165/00002512-200219060-00002.
• Asthana S, Baker LD, Craft S, Stanczyk FZ, Veith RC, Raskind MA, Plymate SR. High-dose estradiol improves cognition for women with AD: results of a randomized study. Neurology. 2001 Aug 28;57(4):605-12. doi: 10.1212/wnl.57.4.605.
• Asthana S, Craft S, Baker LD, Raskind MA, Birnbaum RS, Lofgreen CP, Veith RC, Plymate SR. Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study. Psychoneuroendocrinology. 1999 Aug;24(6):657-77. doi: 10.1016/s0306-4530(99)00020-7.

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: August 4, 2003
• First Submitted That Met QC Criteria: August 4, 2003
• First Posted (Estimate): August 5, 2003

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer disease; Postmenopausal women; Hormone replacement therapy
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Contraceptive Agents, Male; Estradiol; Progesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Estrogens; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 2001-477; R01AG017196-03 (U.S. NIH Grant/Contract); FDA IRB approval M1285; NIH grant AG17196-03; IA0048 (Other Identifier: Study Team)