Menopausal SyndromeR21NCT01046643
Early Menopause Hormone Treatment and Cognition
A study testing Estradiol (E2), Progesterone (P10) x90 and Progesterone (P10) x10 in people with Menopausal Syndrome, run by University of Michigan at 1 site in United States.
Trial summary
The objective of this study is to evaluate the neurobiological effects of hormone therapy (HT) in healthy early postmenopausal women. The studies proposed in this project seek to define the association between different hormone forms (estradiol only and progesterone only) versus placebo on brain functional measures. Read more about this study
- Who is it for?
- Ages 45 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopausal Syndrome
- What is being tested?
- Estradiol (E2), Progesterone (P10) x90 and Progesterone (P10) x10
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Mar 2012
- 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 45 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Postmenopausal women
- Ages 45-55, 6 - 36 months from their last menstrual period.
Who cannot join
- Left handedness
- Acute medical illness
- Neurologic illness
- Psychiatric illness
- Heart disease
- Thromboembolic disease
Show all 31Show fewer
- Liver disease
- Uncorrected thyroid disease
- Diabetes
- Neurological disease
- Porphyria
- Allergy to estradiol
- Progesterone or lactose
- Lactose intolerance
- Claustrophobia
- Contraindications to MRI (including pacemakers, surgical clips or metallic surgical devices)
- Smoking within the last 3 years
- Use of hormones within the last 3 months
- Current or past history of substance abuse
- History of head injury or loss of consciousness
- Medications with actions on the central nervous system
- Endometrial lining greater than 5mm
- Ovarian pathology on ultrasound
- Abnormal mammogram
- Migraines
- Fasting cholesterol >300 mg/dl, and fasting triglycerides >300 mg/dl
- Creatinine level > 1.5 mg/dl
- Aspartate transaminase (AST) or Alanine transaminase (ALT) greater than two times the top normal range
- Follicle stimulating hormone (FSH) values <40 IU/L
- estradiol >40 pg/ml.
- Subjects with HAM-D score > 8, HAM-A > 6 during screening will not be eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan
Ann Arbor, Michigan, 48109
About this study
Official title: Hormones and Cognitive Processing in Early Postmenopausal Women
The objective of this study is to evaluate the neurobiological effects of hormone therapy (HT) in healthy early postmenopausal women. The studies proposed in this project seek to define the association between different hormone forms (estradiol only and progesterone only) versus placebo on brain functional measures. The functional measures will include the performance of the volunteers on a comprehensive neuropsychological testing battery, and the brain functional responses to episodic memory (verbal and non-verbal) challenges as well as emotional processing determined with functional magnetic resonance imaging (fMRI).
Read the detailed description
Specific Aims
Aim 1. To examine the effects of estradiol alone on brain functioning in early post-menopausal women during verbal and non-verbal cognitive tasks.
Hypothesis: It is expected that with estradiol treatment brain activation will be more prominent in the hippocampus and prefrontal cortical areas compared to placebo. The magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.
Aim 2. To determine the effects of progesterone alone on brain functioning in early postmenopausal women during verbal and non-verbal cognitive tasks.
Hypothesis: It is expected that with progesterone treatment brain activation in the hippocampus and prefrontal cortical areas will be decreased compared to both the placebo condition (within subjects) and the estradiol condition (between subjects). Interindividual variations in the magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.
Aim 3. To determine the individual effects of estradiol and progesterone on brain functioning in early postmenopausal women during emotional processing stimuli.
Hypothesis: During negative stimuli estradiol-treated women compared to placebo group, are expected to have increased activity in the amygdala, posterior cingulate, and orbitofrontal cortex, while in progesterone-treated women compared to placebo, decreased activity is expected in these brain regions.
- Conditions
- Menopausal Syndrome
- Being tested
- Estradiol (E2), Progesterone (P10) x90, Progesterone (P10) x10
- Keywords
- Women, Healthy, Menopausal, Hormone treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol (E2)Drug
Also called E2
One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days; followed by one Progesterone (200mg) once a day, at the same time each day, for 10 days to slough endometrial lining; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Progesterone (P10) x90Drug
Also called P10
One Progesterone capsule (200mg) once a day, at the same time each day, for 90 days; followed by one Placebo capsule (to mirror Progesterone capsule to slough endometrial lining in Estradiol recipients) once a day, at the same time each day, for 10 days ; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Progesterone (P10) x10Drug
Also called P10
One Progesterone (200mg) capsule once a day for 10 days, to slough endometrial lining for patients taking Estradiol. Patients taking Progesterone will take an equivalent Placebo capsule during this time period.
| Study group | Role | What they receive |
|---|---|---|
| Estrogen followed by Placebo | Active comparator | Estrogen treatment with Estradiol (E2) followed by Placebo. Receives: Drug: Estradiol (E2); Drug: Progesterone (P10) x10 |
| Progesterone followed by Placebo | Active comparator | Progesterone (P10) treatment followed by Placebo. Receives: Drug: Progesterone (P10) x90 |
| Placebo followed by Estrogen | Active comparator | Placebo followed by Estrogen treatment with Estradiol (E2) Receives: Drug: Estradiol (E2); Drug: Progesterone (P10) x10 |
| Placebo followed by Progesterone | Active comparator | Placebo followed by Progesterone (P10) treatment. Receives: Drug: Progesterone (P10) x90 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo.
The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing).
The test was administered 3 months after baseline and 38 weeks after baseline.
Measured: August 2010 - March 2012
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Measure the changes in brain activity in visual tasks with hormone use (either estradiol or progesterone) versus placebo.
The test is a visual working memory task, where the women are presented with 3 geometric grids on the screen. The target grid is on top, and 2 test grids are on the bottom. The women must decide if the right or left test grid matches the grid on top. There are 3 conditions: a match condition where all 3 grids are shown simultaneously, and 2 delay conditions, where the target grid is shown first, disappears, and the test grids appear after a 1 or a 4 second delay.
The test was administered 3 months after baseline and 38 weeks after baseline.
Measured: August 2010 - March 2012
Secondary outcomes (2)
Neuropsychological Testing Scores - Verbal Learning Retention
Changes in neuropsychological testing measures (verbal learning retention) with hormone use (either estradiol or progesterone) versus placebo.
Subjects are given tests that present them with a series of words. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the Benton Visual Memory Test, Revised.
The tests were administered 3 months after baseline and 38 weeks after baseline.
Measured: August 2010 - March 2012
Neuropsychological Testing Scores - Visual Learning Retention
Changes in neuropsychological testing measures (visual learning retention) with hormone use (either estradiol or progesterone) versus placebo.
Subjects are given tests that present them with a series of pictures. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the California Verbal Learning Test - 2nd edition.
The tests were administered 3 months after baseline and 38 weeks after baseline.
Measured: August 2010 - March 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2010 (estimated)
- Study startMay 2010
- Primary completionMar 2012
- Study completionMar 2012
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 Menopausal SyndromeStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Yolanda Smith, M.D., University of Michigan
- Investigators
- Yolanda R. Smith, M.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01046643
- Sponsor's protocol ID
- 1R21AG031951-01A1
- Other IDs
- 1R21AG031951-01A1
- Acronym
- R21
- Status last verified
- May 2014
- First submitted
- 11 Jan 2010
- Last updated
- 19 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hormones and Cognitive Processing in Early Postmenopausal Women
- ClinicalTrials.gov ID
- NCT01046643
- Acronym / sponsor ID
- R21 / 1R21AG031951-01A1
- Conditions
- Menopausal Syndrome
- Keywords
- Women, Healthy, Menopausal, Hormone treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- May 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 12 Jan 2010 (estimated)
- Results
- Posted 19 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to evaluate the neurobiological effects of hormone therapy (HT) in healthy early postmenopausal women. The studies proposed in this project seek to define the association between different hormone forms (estradiol only and progesterone only) versus placebo on brain functional measures. The functional measures will include the performance of the volunteers on a comprehensive neuropsychological testing battery, and the brain functional responses to episodic memory (verbal and non-verbal) challenges as well as emotional processing determined with functional magnetic resonance imaging (fMRI).
Detailed description
Specific Aims
Aim 1. To examine the effects of estradiol alone on brain functioning in early post-menopausal women during verbal and non-verbal cognitive tasks.
Hypothesis: It is expected that with estradiol treatment brain activation will be more prominent in the hippocampus and prefrontal cortical areas compared to placebo. The magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.
Aim 2. To determine the effects of progesterone alone on brain functioning in early postmenopausal women during verbal and non-verbal cognitive tasks.
Hypothesis: It is expected that with progesterone treatment brain activation in the hippocampus and prefrontal cortical areas will be decreased compared to both the placebo condition (within subjects) and the estradiol condition (between subjects). Interindividual variations in the magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.
Aim 3. To determine the individual effects of estradiol and progesterone on brain functioning in early postmenopausal women during emotional processing stimuli.
Hypothesis: During negative stimuli estradiol-treated women compared to placebo group, are expected to have increased activity in the amygdala, posterior cingulate, and orbitofrontal cortex, while in progesterone-treated women compared to placebo, decreased activity is expected in these brain regions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Estrogen followed by Placebo | Active comparator | Drug: Estradiol (E2), Drug: Progesterone (P10) x10Estrogen treatment with Estradiol (E2) followed by Placebo. |
| Progesterone followed by Placebo | Active comparator | Drug: Progesterone (P10) x90Progesterone (P10) treatment followed by Placebo. |
| Placebo followed by Estrogen | Active comparator | Drug: Estradiol (E2), Drug: Progesterone (P10) x10Placebo followed by Estrogen treatment with Estradiol (E2) |
| Placebo followed by Progesterone | Active comparator | Drug: Progesterone (P10) x90Placebo followed by Progesterone (P10) treatment. |
Who may qualify
- Ages
- 45 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Postmenopausal women
- Ages 45-55, 6 - 36 months from their last menstrual period.
Key exclusion criteria (31 listed)
- Left handedness
- Acute medical illness
- Neurologic illness
- Psychiatric illness
- Heart disease
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 |
|---|---|---|
| Estradiol (E2)Also: E2One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days; followed by one Progesterone (200mg) once a day, at the same time each day, for 10 days to slough endometrial lining; followed by one Placebo capsule once a day, at the same time each day, for 90 days. | Drug | Estrogen followed by Placebo, Placebo followed by Estrogen |
| Progesterone (P10) x90Also: P10One Progesterone capsule (200mg) once a day, at the same time each day, for 90 days; followed by one Placebo capsule (to mirror Progesterone capsule to slough endometrial lining in Estradiol recipients) once a day, at the same time each day, for 10 days ; followed by one Placebo capsule once a day, at the same time each day, for 90 days. | Drug | Placebo followed by Progesterone, Progesterone followed by Placebo |
| Progesterone (P10) x10Also: P10One Progesterone (200mg) capsule once a day for 10 days, to slough endometrial lining for patients taking Estradiol. Patients taking Progesterone will take an equivalent Placebo capsule during this time period. | Drug | Estrogen followed by Placebo, Placebo followed by Estrogen |
Primary outcome
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Time frame: August 2010 - March 2012
Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing). The test was administered 3 months after baseline and 38 weeks after baseline.
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Time frame: August 2010 - March 2012
Measure the changes in brain activity in visual tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a visual working memory task, where the women are presented with 3 geometric grids on the screen. The target grid is on top, and 2 test grids are on the bottom. The women must decide if the right or left test grid matches the grid on top. There are 3 conditions: a match condition where all 3 grids are shown simultaneously, and 2 delay conditions, where the target grid is shown first, disappears, and the test grids appear after a 1 or a 4 second delay. The test was administered 3 months after baseline and 38 weeks after baseline.
2 secondary outcomes
Neuropsychological Testing Scores - Verbal Learning Retention
Time frame: August 2010 - March 2012
Neuropsychological Testing Scores - Visual Learning Retention
Time frame: August 2010 - March 2012
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
- 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.
Yolanda R. Smith, M.D. principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Estradiol (E2), Progesterone (P10) x90 and Progesterone (P10) x10 in people with Menopausal Syndrome, run by University of Michigan at 1 site 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 2 inclusion and 31 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 19 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 19 May 2014). 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 Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans (time frame: August 2010 - March 2012). 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 19 May 2014.