Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women

NCT ID: NCT02122198

Last Updated: 2022-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-08
• Study Completion Date: 2017-09-15

Brief Summary

Complaints about memory and thinking are common in women as they go through menopause and estrogen levels fall. The ovarian hormone estrogen is important for supporting normal cognitive function, and changes in brain activity and function occur when estrogen levels are decreased. Estrogen is also important for maintaining healthy blood vessels which also support normal cognitive function. In Alzheimer's disease and other types of dementia, there is significant damage to the blood vessels in the brain. This study will test whether changes in brain activity and function with the loss of estrogen are related to changes in vascular function. The investigators will measure vascular function using ultrasound, and brain activity using MRI scans in women who are enrolled in the Females, Aging, Metabolism and Exercise (FAME) study (NCT01712230). In the FAME study, healthy premenopausal women either take a medication to decrease their estrogen levels, or a placebo. This sub-study may provide new information about how estrogen affects vascular function and cognitive function, and lead to new ways to prevent or delay cognitive impairment or dementia.

Conditions

Cognitive Impairment; Executive Dysfunction; Endothelial Dysfunction; Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

GnRH agonist

Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol.

Weekly application of estradiol patch 0.075mg/d months 6-9.

Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30.

Group Type: ACTIVE_COMPARATOR

Leuprolide acetate

Intervention Type: DRUG

Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study.

Estradiol

Intervention Type: DRUG

Climara transdermal patch 0.075mg/day applied weekly months 6-9

Medroxyprogesterone

Intervention Type: DRUG

Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.

Interventions

Leuprolide acetate

Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study.

Intervention Type: DRUG

Estradiol

Climara transdermal patch 0.075mg/day applied weekly months 6-9

Intervention Type: DRUG

Medroxyprogesterone

Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

Other Intervention Names

Lupron; Climara; Provera

Eligibility Criteria

Inclusion Criteria

1. Volunteers will be healthy women aged 40 to 60 years

2. Are enrolled in the parent FAME study (NCT01712230).

The Investigators will consent up to 80 subjects with the aim of enrolling 17 in each of the 2 groups (placebo, GnRH agonist).

Exclusion Criteria

1. mini-mental state examination (MMSE) score 27 or less

2. history of neurologic disease or major psychiatric illness

3. major depressive episode within the past 12 months

4. history of learning disability

5. less than high-school education

6. current smoking

7. use of psychoactive medications in the past 3 months (stable use of anti- depressant medication is allowed)

8. contraindications to MRI scanning

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kerry L Hildreth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

University of Colorado Boulder Intermountain Neuroimaging Consortium

Boulder, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UL1TR001082

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14-0193

Identifier Type: -

Identifier Source: org_study_id