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

Cardiovascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02122198
• Other study ID #: 14-0193
• Secondary ID: UL1TR001082
• Status: Completed
• Phase: N/A
• Start date: September 8, 2014
• Est. completion date: September 15, 2017

Study information

• Verified date: December 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 15, 2017
• Est. primary completion date: May 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Cognitive Dysfunction
• Cognitive Impairment
• Endothelial Dysfunction
• Executive Dysfunction

Intervention

Drug:
• 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.
• Estradiol
Climara transdermal patch 0.075mg/day applied weekly months 6-9
• Medroxyprogesterone
Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
• Placebo
placebo

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	University of Colorado Boulder Intermountain Neuroimaging Consortium	Boulder	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Changes in Endothelial Function at 6 Months	Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 6 months	Baseline, 6 months
Secondary	Changes in Endothelial Function at 9 Months	Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 9 months	Baseline, 9 months
Secondary	Changes in Artery Compliance at 6 Months	Changes in carotid artery compliance will be measured using ultrasound in at baseline, 6 months.	Baseline, 6 months
Secondary	Changes in Artery Compliance at 9 Months	Changes in carotid artery compliance will be measured using ultrasound in at baseline, 9 months.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: Trails A, 6 Months	Change in time (seconds) to complete Trails A test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: Trails A, 9 Months	Change in time (seconds) to complete Trails A test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: RAVLT, 6 Months	Change in Rey Auditory Verbal Learning Test from baseline to 6 months.; Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: RAVLT, 9 Months	Change in Rey Auditory Verbal Learning Test from baseline to 9 months.; Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: Trails B, 6 Months	Change in time (seconds) to complete Trails B test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: Trails B, 9 Months	Change in time (seconds) to complete Trails B test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: Stroop, 6 Months	Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 6 months. A positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: Stroop, 9 Months	Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 9 months. Positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: Digits Span Forward and Backward, 6 Months	Change in score on the Digit Span Test between baseline and 6 month. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: Digits, 9 Months	Change in score on the Digit Span Test between baseline and 9 months. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.	Baseline, 9 months
Secondary	Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 6 Months	Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 6 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.	Baseline, 6 months
Secondary	Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 9 Months	Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 9 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.	Baseline, 9 months