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

NCT02122198 | Completed Results

• 2 other identifiers: 14-0193UL1TR001082
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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

Keywords

Cognitive impairment; Executive function; Arterial stiffness; Endothelial function; Menopause; Women's health; Hormone therapy; functional MRI

Outcome Measures

Primary Outcomes (2)

• Changes in Prefrontal Cortex Brain Activation at 6 Months

  Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.

  Baseline, 6 months

• Changes in Prefrontal Cortex Brain Activation at 9 Months

  Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.

  Baseline, 9 months

Secondary Outcomes (16)

• Changes in Endothelial Function at 6 Months

  Baseline, 6 months

• Changes in Endothelial Function at 9 Months

  Baseline, 9 months

• Changes in Artery Compliance at 6 Months

  Baseline, 6 months

• Changes in Artery Compliance at 9 Months

  Baseline, 9 months

• Changes in Executive Cognitive Function: Trails A, 6 Months

  Baseline, 6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

GnRH agonist

ACTIVE COMPARATOR

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.

Drug: Leuprolide acetate; Drug: Estradiol; Drug: Medroxyprogesterone

Interventions

Leuprolide acetate 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.

Also known as: Lupron

GnRH agonist

Estradiol DRUG

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

Also known as: Climara

GnRH agonist

Medroxyprogesterone DRUG

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

Also known as: Provera

GnRH agonist

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 40 Years - 60 Years
• Gender Eligibility Details: Healthy women aged 40 to 60 years.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteers will be healthy women aged 40 to 60 years
• 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).

You may not qualify if:

• mini-mental state examination (MMSE) score 27 or less
• history of neurologic disease or major psychiatric illness
• major depressive episode within the past 12 months
• history of learning disability
• less than high-school education
• current smoking
• use of psychoactive medications in the past 3 months (stable use of anti- depressant medication is allowed)
• contraindications to MRI scanning

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (2)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Colorado Boulder Intermountain Neuroimaging Consortium

Boulder, Colorado, 80309, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Cardiovascular Diseases

Interventions

Leuprolide; Estradiol; Medroxyprogesterone; Medroxyprogesterone Acetate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes

Results Point of Contact

• Title: Kerry Hildreth, MD
• Organization: University of Colorado Denver

clinicalresearchsupportcenter@ucdenver.edu

3037241111

Study Officials

• Kerry L Hildreth, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: September 8, 2014
• Primary Completion: May 30, 2017
• Study Completion: September 15, 2017
• Last Updated: January 10, 2022
• Results First Posted: January 10, 2022

Record last verified: 2021-12

Locations

US (2)