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Aging and Estrogen on Cortical Function

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ClinicalTrials.gov Identifier: NCT01268046
Recruitment Status : Completed
First Posted : December 29, 2010
Results First Posted : August 22, 2018
Last Update Posted : August 22, 2018
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Memory Loss Cognitive Changes Postmenopausal Symptoms Drug: Estradiol oral capsule Drug: transderman estrogen patch Drug: trasdermal placebo patch Drug: placebo oral capsule Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Each participant was randomized to placebo or estrogen using a block randomized design by age group
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Randomization was performed by the Research Pharmacy and the investigative team was blinded.
Primary Purpose: Other
Official Title: The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.
Actual Study Start Date : November 2009
Actual Primary Completion Date : December 2, 2013
Actual Study Completion Date : December 2, 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory
Drug Information available for: Estrogens

Arm Intervention/treatment
Experimental: Young postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
Drug: Estradiol oral capsule
1 oral capsule (1 mg estradiol) administered daily for one month
Other Names:
  • Micronized Estradiol
  • Estradiol

Drug: transderman estrogen patch
transdermal estrogen patch (50 mcg/day) for one month
Other Names:
  • Climara
  • Estraderm
  • Estrogen patch

Experimental: Older postmenopausal women - estrogen
transdermal estrogen patch OR estradiol oral capsule for 1 month
Drug: Estradiol oral capsule
1 oral capsule (1 mg estradiol) administered daily for one month
Other Names:
  • Micronized Estradiol
  • Estradiol

Drug: transderman estrogen patch
transdermal estrogen patch (50 mcg/day) for one month
Other Names:
  • Climara
  • Estraderm
  • Estrogen patch

Placebo Comparator: Young postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
Drug: trasdermal placebo patch
transdermal placebo patch with patch change every 84 hr for one month
Other Name: Placebo patch

Drug: placebo oral capsule
placebo oral capsule administered daily for one month.
Other Name: Placebo capsule

Placebo Comparator: Older postmenopausal women - placebo
transdermal placebo patch for 1 month or placebo oral capsule for 1 month
Drug: trasdermal placebo patch
transdermal placebo patch with patch change every 84 hr for one month
Other Name: Placebo patch

Drug: placebo oral capsule
placebo oral capsule administered daily for one month.
Other Name: Placebo capsule




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. young postmenopausal (age 45-55) or older (age 65-80) postmenopausal women
  2. 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
  3. prescription hormone replacement treatment discontinued at least 3 months before study
  4. Normal or corrected normal vision
  5. Intelligence quotient (IQ) > 70 on the Wechsler Adult Reading Test (WTAR)*
  6. Absence of Mild Cognitive Impairment (MCI) and depression on the Mini Mental State Examination (MMSE)** and Beck Depression Inventory II (BDI-II).***
  7. Normal mammogram or breast MRI within the past 2 years

Exclusion Criteria

  1. On gonadal hormone replacement medication, herbal supplements and/or over the counter menopause treatment within three months of study
  2. History of radiotherapy or chemotherapy.
  3. Absolute contraindications to the use of physiologic replacement doses of estrogen and/or history of coronary artery disease
  4. History of breast cancer, blood clot, pulmonary embolus, hypercoagulability and stroke.
  5. On centrally acting medications
  6. History of head trauma and/or neurologic disorder
  7. Contraindication to MRI (eg. metal implants) or PET imaging (eg. PET imaging studies in the previous 12 months)
  8. Concurrent participation in research studies involving medications and/or PET scans.
  9. Left handedness.
  10. Current breast lump(s) or family/genetic history of breast cancer in younger women (< 40 years old).
  11. Current smoking

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01268046


Locations
United States, Massachusetts
Reproductive Endocrine Unit, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institute on Aging (NIA)
Investigators
Principal Investigator: Janet E Hall, MD Massachusetts General Hospital

Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01268046     History of Changes
Other Study ID Numbers: 2009P-002311
R01AG013241 ( U.S. NIH Grant/Contract )
First Posted: December 29, 2010    Key Record Dates
Results First Posted: August 22, 2018
Last Update Posted: August 22, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified information will be made available on request to the PI once the primary data analysis has been published.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: From time of publication of initial 2 manuscripts (December 2019) for 5 years
Access Criteria: Academic investigator with funding for analysis, approval of PI

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Janet E. Hall, MD, Massachusetts General Hospital:
aging
postmenopausal women
estrogen
memory

Additional relevant MeSH terms:
Memory Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female