Effects of Estrogen on Memory in Post-Menopausal Women and Patients With Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT00006399
• Recruitment Status: Completed
• First Posted: August 21, 2000
• Last Update Posted: January 15, 2009
• Sponsor: National Center for Research Resources (NCRR)
• Collaborators: Alzheimer's Association; Pfizer; Eisai Inc.
• Information provided by: National Institute on Aging (NIA)

Study Description

Brief Summary:

The goal of this study is to examine whether the administration of estrogen to post-menopausal women and women with mild to moderate Alzheimer's disease will enhance their memory and their capacity for learning.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: Donepezil; Drug: Estrogen; Drug: Progesterone	Phase 2

Detailed Description:

Estrogen (EST) may have significant benefits in preserving cognitive functioning in normal aging after menopause and in decreasing the incidence of Alzheimer's disease (AD). On a molecular level, EST has effects on a variety of cholinergic neuronal and receptor-mediated mechanisms that may be responsible for these beneficial effects. These neurons have critical relevance for the development of age-related cognitive changes and dementing disorders. However, little is known about the clinical relevance of EST-cholinergic interactions, either in normal aging or in AD.

The primary goal of this study is to test the hypothesis that three months of administration of EST to 1) normal post-menopausal women, and 2) female patients with mild-moderate AD who are concurrently treated with anticholinesterase therapy (donepezil), will positively change or blunt the negative and behavioral effects of drugs that block central cholinergic receptors (both muscarinic and nicotinic). Participants will be blindly placed on EST or placebo for three months each. After each three month period, they will be cognitively assessed after receiving single doses of the cholinergic antagonists scopolamine and mecamylamine. These results will have direct implications for the use of EST in post-menopausal women as well as interactive treatment with cholinergic drugs for AD. Researchers plan to recruit a total of 45 women (30 healthy, and 15 patients with AD).

NOTE: This study is only recruiting participants with Alzheimer's Disease at this time.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 45 participants
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Estrogen Modulation Effects on Cholinergic Function in Normal Post-Menopausal Women and Patients With Alzheimer's Disease
• Study Start Date: September 1999
• Actual Primary Completion Date: March 2004
• Actual Study Completion Date: March 2004

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Normal volunteers and women with mild Alzheimer's disease:
• Non-smoker
• No use of Hormone Replacement Therapy for at least one year
• No menses for at least one year
• Normal mammogram within the last year
• minimum age is 45 for patients with Alzheimer's disease; 50 for normal volunteers
• Maximum age is 85 for patients with Alzheimer's disease; there is no maximum age for normal volunteers.

Exclusion Criteria:

• Women who are currently taking estrogen therapy.
• Women who are smokers.
• Women who have had breast cancer.

Contacts and Locations

Locations

United States, Vermont

Clinical Neuroscience Research Unit, University of Vermont

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

National Center for Research Resources (NCRR)

Alzheimer's Association

Pfizer

Eisai Inc.

Investigators

• Principal Investigator: Paul A. Newhouse, M.D.; Memory Center, Department of Psychiatry, University of Vermont College of Medicine

More Information

Additional Information:

University of Vermont, Clinical Neuroscience Research Unit 

Publications:

Newhouse PA, Potter A, Corwin J, Lenox R. Acute nicotinic blockade produces cognitive impairment in normal humans. Psychopharmacology (Berl). 1992;108(4):480-4. doi: 10.1007/BF02247425.

Newhouse PA, Potter A, Corwin J, Lenox R. Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior. Neuropsychopharmacology. 1994 Apr;10(2):93-107. doi: 10.1038/npp.1994.11.

Newhouse PA, Potter A, Corwin J, Lenox, R. Effects of nicotinic cholinergic agents on cognitive functioning in Alzheimer's and Parkinson's disease. Drug Development Research 38:278-289, 1996.

• Responsible Party: Paul A. Newhouse, M.D, Department of Psychiatry, University of Vermont College of Medicine
• ClinicalTrials.gov Identifier: NCT00006399
• Other Study ID Numbers: IA0023; 2R56AG021476 ( U.S. NIH Grant/Contract )
• First Posted: August 21, 2000
• Last Update Posted: January 15, 2009
• Last Verified: January 2009

Keywords provided by National Institute on Aging (NIA):

Alzheimer disease; Estrogen therapy; Post-menopausal women

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Donepezil; Progesterone; Estrogens; Progestins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Nootropic Agents