Cognitive ImpairmentNCT02122198
Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women
A study testing Leuprolide acetate, Estradiol and Medroxyprogesterone in people with Cognitive Impairment and Executive Dysfunction, run by University of Colorado, Denver at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cognitive Impairment, Executive Dysfunction, Endothelial Dysfunction
- What is being tested?
- Leuprolide acetate, Estradiol and Medroxyprogesterone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Sep 2014to 15 Sep 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
University of Colorado Boulder Intermountain Neuroimaging Consortium
Boulder, Colorado, 80309
About this study
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
- Being tested
- Leuprolide acetate, Estradiol, Medroxyprogesterone, Placebo
- Keywords
- Cognitive impairment, Executive function, Arterial stiffness, Endothelial function, Menopause, Women's health, Hormone therapy, functional MRI
- Medical subject headings
- Cognitive Dysfunction, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Leuprolide acetateDrug
Also called Lupron
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.
EstradiolDrug
Also called Climara
Climara transdermal patch 0.075mg/day applied weekly months 6-9
MedroxyprogesteroneDrug
Also called Provera
Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Receives: 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. Receives: Drug: Leuprolide acetate; Drug: Estradiol; Drug: Medroxyprogesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline, 9 months
Secondary outcomes (16)
Changes in Endothelial Function at 6 Months
Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 6 months
Measured: Baseline, 6 months
Changes in Endothelial Function at 9 Months
Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 9 months
Measured: Baseline, 9 months
Changes in Artery Compliance at 6 Months
Changes in carotid artery compliance will be measured using ultrasound in at baseline, 6 months.
Measured: Baseline, 6 months
Changes in Artery Compliance at 9 Months
Changes in carotid artery compliance will be measured using ultrasound in at baseline, 9 months.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
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.
Measured: Baseline, 6 months
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.
Measured: Baseline, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study start8 Sep 2014
- Primary completion30 May 2017
- Study completion15 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kerry L Hildreth, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02122198
- Sponsor's protocol ID
- 14-0193
- Other IDs
- UL1TR001082
- Status last verified
- Dec 2021
- First submitted
- 22 Apr 2014
- Last updated
- 10 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women
- ClinicalTrials.gov ID
- NCT02122198
- Acronym / sponsor ID
- 14-0193
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 8 Sep 2014 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 15 Sep 2017 (actual)
- First posted
- 24 Apr 2014 (estimated)
- Results
- Posted 10 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMonthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) |
| GnRH agonist | Active comparator | Drug: Leuprolide acetate, Drug: Estradiol, Drug: MedroxyprogesteroneMonthly 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. |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leuprolide acetateAlso: LupronLupron 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. | Drug | GnRH agonist |
| EstradiolAlso: ClimaraClimara transdermal patch 0.075mg/day applied weekly months 6-9 | Drug | GnRH agonist |
| MedroxyprogesteroneAlso: ProveraProvera 5mg tablets once daily by mouth for 12 days beginning at week 30. | Drug | GnRH agonist |
| Placeboplacebo | Drug | Placebo |
Primary outcome
Changes in Prefrontal Cortex Brain Activation at 6 Months
Time frame: Baseline, 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.
Changes in Prefrontal Cortex Brain Activation at 9 Months
Time frame: Baseline, 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.
16 secondary outcomes
Changes in Endothelial Function at 6 Months
Time frame: Baseline, 6 months
Changes in Endothelial Function at 9 Months
Time frame: Baseline, 9 months
Changes in Artery Compliance at 6 Months
Time frame: Baseline, 6 months
Changes in Artery Compliance at 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Trails A, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Trails A, 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: RAVLT, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: RAVLT, 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Trails B, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Trails B, 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Stroop, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Stroop, 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Digits Span Forward and Backward, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Digits, 9 Months
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 6 Months
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 9 Months
Time frame: Baseline, 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kerry L Hildreth, MD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Leuprolide acetate, Estradiol and Medroxyprogesterone in people with Cognitive Impairment and Executive Dysfunction, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Prefrontal Cortex Brain Activation at 6 Months (time frame: Baseline, 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2022.