Alzheimer's Disease: Therapeutic Potential of Estrogen

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT00066157
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 42
• Location: 1
• Arms: 4
• Duration (Months): 75
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Transdermal estradiol; Drug: Medroxyprogesterone; Drug: Placebo Patch; Drug: Placebo	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Alzheimer's Disease: Therapeutic Potential of Estrogen
• Study Start Date: Sep 1, 2001
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

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: 17 (beta) estradiol transdermal patch Estrogen replacement therapy ; 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: 17 (beta) estradiol transdermal patch Estrogen replacement therapy ; 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 Patch; Transdermal placebo patch, changed every 3 days, for 12 months; Drug: Placebo; Placebo tablet daily for 12 months

Outcome Measures

Primary Outcome Measures

1. 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

1. Skills of Independent Living: Physical functioning Performance (PFP) [Baseline and 1, 3, 6, 12, and 15 months]

2. Bioassays (Estradiol, estrone, medroxyprogesterone, FSH, influence of ApoE genotype in responsivity to estrogen) [Baseline and 1, 3, 6, 12, and 15 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Memory Research Program	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• University of Wisconsin, Madison
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Sanjay Asthana, MD, University of Wisconsin - Madison, William S. Middleton VA Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• Cholerton B, Gleason CE, Baker LD, Asthana S. Estrogen and Alzheimer's disease: the story so far. Drugs Aging. 2002;19(6):405-27. Review.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00066157
• Other Study ID Numbers: 2001-477; R01AG017196-03; FDA IRB approval M1285; NIH grant AG17196-03; IA0048
• First Posted: Aug 5, 2003
• Last Update Posted: Aug 23, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by University of Wisconsin, Madison: Alzheimer disease; Hormone replacement therapy; Postmenopausal women
• Additional relevant MeSH terms: Alzheimer Disease; Medroxyprogesterone Acetate; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Medroxyprogesterone; Estradiol; Polyestradiol phosphate; Estrogens; Progesterone

Study Results

No Results Posted as of Aug 23, 2018