Memory LossPhase 1/2NCT01268046
Aging and Estrogen on Cortical Function
A Phase 1/2 study testing Estradiol oral capsule and transderman estrogen patch in people with Memory Loss and Cognitive Changes, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study will focus on how estrogen affects parts of the brain associated with memory and how the effect of estrogen is altered with aging in postmenopausal women. Read more about this study
- Who is it for?
- Ages 45 to 80 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Memory Loss, Cognitive Changes, Postmenopausal Symptoms
- What is being tested?
- Estradiol oral capsule and transderman estrogen patch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to 2 Dec 2013
- Phase
- Phase 1/2
- 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 80 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- young postmenopausal (age 45-55) or older (age 65-80) postmenopausal women
- otherwise healthy, non-obese women with normal blood pressure and a history of normal menopause, defined by the absence of menses for at least 12 months
- prescription hormone replacement treatment discontinued at least 3 months before study
- Normal or corrected normal vision
- Intelligence quotient (IQ) > 70 on the Wechsler Adult Reading Test (WTAR)*
- Absence of Mild Cognitive Impairment (MCI) and depression on the Mini Mental State Examination (MMSE) and Beck Depression Inventory II (BDI-II).*
- Normal mammogram or breast MRI within the past 2 years
Who cannot join
- On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment within three months of study
- History of radiotherapy or chemotherapy.
- Absolute contraindications to the use of physiologic replacement doses of estrogen and/or history of coronary artery disease
- History of breast cancer, blood clot, pulmonary embolus, hypercoagulability and stroke.
- On centrally acting medications
- History of head trauma and/or neurologic disorder
Show all 11Show fewer
- Contraindication to MRI (eg. metal implants) or PET imaging (eg. PET imaging studies in the previous 12 months)
- Concurrent participation in research studies involving medications and/or PET scans.
- Left handedness.
- Current breast lump(s) or family/genetic history of breast cancer in younger women (< 40 years old).
- Current smoking
Trial locations and contacts
1 site in 1 country.
United States1 site
Reproductive Endocrine Unit, Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.
This study will focus on how estrogen affects parts of the brain associated with memory and how the effect of estrogen is altered with aging in postmenopausal women.
Read the detailed description
The broad goal of this proposal is to determine the effect of aging on areas of the brain whose function is impacted by gonadal steroids in women. The overarching hypothesis is that aging differentially alters the effects of estrogen on the brain. Our preliminary data indicated that aging alters the effect of estrogen on brain regions involved in cognition and thus, the current study focused on the impact of aging on functional changes induced by estrogen in cortical and subcortical areas associated with verbal working memory and declarative/episodic memory.
As our model, we will use women in whom the absence of gonadal function makes it possible to control the duration and amount of estrogen exposure, specifically postmenopausal women who are younger (45-55) or older (65-80) who receive either oral or transdermal estradiol to achieve premenopausal early follicular phase estradiol levels.. We evaluate the effects of low dose estrogen exposure at 48 hr and 1 month to determine whether the short-term changes in brain regions involved in cognition with low dose estrogen exposure seen in our preliminary studies are confirmed and whether changes with short-term estrogen exposure persist with more prolonged exposure, a finding that would have enormous clinical relevance. These studies, using sophisticated neuroimaging tools (structural and functional magnetic resonance imaging [MRI] and [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography [FDG-PET]), provide a unique window into the brain in women.
- Conditions
- Memory Loss, Cognitive Changes, Postmenopausal Symptoms
- Being tested
- Estradiol oral capsule, transderman estrogen patch, trasdermal placebo patch, placebo oral capsule
- Keywords
- aging, postmenopausal women, estrogen, memory
- Medical subject headings
- Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol oral capsuleDrug
Also called Micronized Estradiol, Estradiol
1 oral capsule (1 mg estradiol) administered daily for one month
transderman estrogen patchDrug
Also called Climara, Estraderm, Estrogen patch
transdermal estrogen patch (50 mcg/day) for one month
trasdermal placebo patchDrug
Also called Placebo patch
transdermal placebo patch with patch change every 84 hr for one month
placebo oral capsuleDrug
Also called Placebo capsule
placebo oral capsule administered daily for one month.
| Study group | Role | What they receive |
|---|---|---|
| Young postmenopausal women - estrogen | Experimental | transdermal estrogen patch OR estradiol oral capsule for 1 month Receives: Drug: Estradiol oral capsule; Drug: transderman estrogen patch |
| Older postmenopausal women - estrogen | Experimental | transdermal estrogen patch OR estradiol oral capsule for 1 month Receives: Drug: Estradiol oral capsule; Drug: transderman estrogen patch |
| Young postmenopausal women - placebo | Placebo comparator | transdermal placebo patch for 1 month or placebo oral capsule for 1 month Receives: Drug: trasdermal placebo patch; Drug: placebo oral capsule |
| Older postmenopausal women - placebo | Placebo comparator | transdermal placebo patch for 1 month or placebo oral capsule for 1 month Receives: Drug: trasdermal placebo patch; Drug: placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)
Change in extracted beta coefficients of the blood oxygen level dependent (BOLD) signal response to a cognitive task (N-back) in the DLPFC (x,y,z coordinates = -34 44 16) from baseline to 1 month as a function of aging and estrogen (young vs older and estrogen vs placebo). A positive change indicates an increase in oxygen utilization (inferring increased neuronal functioning) between baseline and treatment during the cognitive task, while a negative change indicates a decrease in oxygen utilization between baseline and treatment during the cognitive task.
Measured: baseline to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2010 (estimated)
- Study startNov 2009
- Primary completion2 Dec 2013
- Study completion2 Dec 2013
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 Memory LossStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each participant was randomized to placebo or estrogen using a block randomized design by age group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Janet E. Hall, MD, Massachusetts General Hospital
- Investigators
- Janet E Hall, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01268046
- Sponsor's protocol ID
- 2009P-002311
- Other IDs
- R01AG013241
- Status last verified
- Jul 2018
- First submitted
- 28 Dec 2010
- Last updated
- 22 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified information will be made available on request to the PI once the primary data analysis has been published.
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.
- ClinicalTrials.gov ID
- NCT01268046
- Acronym / sponsor ID
- 2009P-002311
- Conditions
- Memory Loss, Cognitive Changes, Postmenopausal Symptoms
- Keywords
- aging, postmenopausal women, estrogen, memory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Nov 2009 (actual)
- Primary completion
- 2 Dec 2013 (actual)
- Study completion
- 2 Dec 2013 (actual)
- First posted
- 29 Dec 2010 (estimated)
- Results
- Posted 22 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will focus on how estrogen affects parts of the brain associated with memory and how the effect of estrogen is altered with aging in postmenopausal women.
Detailed description
The broad goal of this proposal is to determine the effect of aging on areas of the brain whose function is impacted by gonadal steroids in women. The overarching hypothesis is that aging differentially alters the effects of estrogen on the brain. Our preliminary data indicated that aging alters the effect of estrogen on brain regions involved in cognition and thus, the current study focused on the impact of aging on functional changes induced by estrogen in cortical and subcortical areas associated with verbal working memory and declarative/episodic memory.
As our model, we will use women in whom the absence of gonadal function makes it possible to control the duration and amount of estrogen exposure, specifically postmenopausal women who are younger (45-55) or older (65-80) who receive either oral or transdermal estradiol to achieve premenopausal early follicular phase estradiol levels.. We evaluate the effects of low dose estrogen exposure at 48 hr and 1 month to determine whether the short-term changes in brain regions involved in cognition with low dose estrogen exposure seen in our preliminary studies are confirmed and whether changes with short-term estrogen exposure persist with more prolonged exposure, a finding that would have enormous clinical relevance. These studies, using sophisticated neuroimaging tools (structural and functional magnetic resonance imaging [MRI] and [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography [FDG-PET]), provide a unique window into the brain in women.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Each participant was randomized to placebo or estrogen using a block randomized design by age group
| Arm | Type | Receives |
|---|---|---|
| Young postmenopausal women - estrogen | Experimental | Drug: Estradiol oral capsule, Drug: transderman estrogen patchtransdermal estrogen patch OR estradiol oral capsule for 1 month |
| Older postmenopausal women - estrogen | Experimental | Drug: Estradiol oral capsule, Drug: transderman estrogen patchtransdermal estrogen patch OR estradiol oral capsule for 1 month |
| Young postmenopausal women - placebo | Placebo comparator | Drug: trasdermal placebo patch, Drug: placebo oral capsuletransdermal placebo patch for 1 month or placebo oral capsule for 1 month |
| Older postmenopausal women - placebo | Placebo comparator | Drug: trasdermal placebo patch, Drug: placebo oral capsuletransdermal placebo patch for 1 month or placebo oral capsule for 1 month |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- young postmenopausal (age 45-55) or older (age 65-80) postmenopausal women
- otherwise healthy, non-obese women with normal blood pressure and a history of normal menopause, defined by the absence of menses for at least 12 months
- prescription hormone replacement treatment discontinued at least 3 months before study
- Normal or corrected normal vision
- Intelligence quotient (IQ) > 70 on the Wechsler Adult Reading Test (WTAR)*
Key exclusion criteria (11 listed)
- On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment within three months of study
- History of radiotherapy or chemotherapy.
- Absolute contraindications to the use of physiologic replacement doses of estrogen and/or history of coronary artery disease
- History of breast cancer, blood clot, pulmonary embolus, hypercoagulability and stroke.
- On centrally acting medications
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 oral capsuleAlso: Micronized Estradiol, Estradiol1 oral capsule (1 mg estradiol) administered daily for one month | Drug | Older postmenopausal women - estrogen, Young postmenopausal women - estrogen |
| transderman estrogen patchAlso: Climara, Estraderm, Estrogen patchtransdermal estrogen patch (50 mcg/day) for one month | Drug | Older postmenopausal women - estrogen, Young postmenopausal women - estrogen |
| trasdermal placebo patchAlso: Placebo patchtransdermal placebo patch with patch change every 84 hr for one month | Drug | Older postmenopausal women - placebo, Young postmenopausal women - placebo |
| placebo oral capsuleAlso: Placebo capsuleplacebo oral capsule administered daily for one month. | Drug | Older postmenopausal women - placebo, Young postmenopausal women - placebo |
Primary outcome
Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)
Time frame: baseline to 1 month
Change in extracted beta coefficients of the blood oxygen level dependent (BOLD) signal response to a cognitive task (N-back) in the DLPFC (x,y,z coordinates = -34 44 16) from baseline to 1 month as a function of aging and estrogen (young vs older and estrogen vs placebo). A positive change indicates an increase in oxygen utilization (inferring increased neuronal functioning) between baseline and treatment during the cognitive task, while a negative change indicates a decrease in oxygen utilization between baseline and treatment during the cognitive task.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified information will be made available on request to the PI once the primary data analysis has been published.
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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.
Janet E Hall, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Estradiol oral capsule and transderman estrogen patch in people with Memory Loss and Cognitive Changes, run by Massachusetts General Hospital 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 7 inclusion and 11 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 22 Aug 2018. 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. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2018). 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?
Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC) (time frame: baseline to 1 month). 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 22 Aug 2018.