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Aging and Estrogen on Cortical Function

Primary Purpose

Memory Loss, Cognitive Changes, Postmenopausal Symptoms

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Estradiol oral capsule

transderman estrogen patch

trasdermal placebo patch

placebo oral capsule

About this trial

This is an interventional other trial for Memory Loss focused on measuring aging, postmenopausal women, estrogen, memory

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria

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
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

Sites / Locations

Reproductive Endocrine Unit, Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Young postmenopausal women - estrogen

Older postmenopausal women - estrogen

Young postmenopausal women - placebo

Older postmenopausal women - placebo

Arm Description

transdermal estrogen patch OR estradiol oral capsule for 1 month

transdermal placebo patch for 1 month or placebo oral capsule for 1 month

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01268046

First Posted

December 28, 2010

Last Updated

July 24, 2018

Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT01268046

Brief Title

Aging and Estrogen on Cortical Function

Official Title

The Effect of Low Dose Estrogen on Cortical Function as a Function of Age in Postmenopausal Women.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

November 2009 (Actual)

Primary Completion Date

December 2, 2013 (Actual)

Study Completion Date

December 2, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Memory Loss, Cognitive Changes, Postmenopausal Symptoms

Keywords

aging, postmenopausal women, estrogen, memory

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Each participant was randomized to placebo or estrogen using a block randomized design by age group

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Randomization was performed by the Research Pharmacy and the investigative team was blinded.

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Young postmenopausal women - estrogen

Arm Type

Experimental

Arm Description

transdermal estrogen patch OR estradiol oral capsule for 1 month

Arm Title

Older postmenopausal women - estrogen

Arm Type

Experimental

Arm Description

transdermal estrogen patch OR estradiol oral capsule for 1 month

Arm Title

Young postmenopausal women - placebo

Arm Type

Placebo Comparator

Arm Description

transdermal placebo patch for 1 month or placebo oral capsule for 1 month

Arm Title

Older postmenopausal women - placebo

Arm Type

Placebo Comparator

Arm Description

transdermal placebo patch for 1 month or placebo oral capsule for 1 month

Intervention Type

Drug

Intervention Name(s)

Estradiol oral capsule

Other Intervention Name(s)

Micronized Estradiol, Estradiol

Intervention Description

1 oral capsule (1 mg estradiol) administered daily for one month

Intervention Type

Drug

Intervention Name(s)

transderman estrogen patch

Other Intervention Name(s)

Climara, Estraderm, Estrogen patch

Intervention Description

transdermal estrogen patch (50 mcg/day) for one month

Intervention Type

Drug

Intervention Name(s)

trasdermal placebo patch

Other Intervention Name(s)

Placebo patch

Intervention Description

transdermal placebo patch with patch change every 84 hr for one month

Intervention Type

Drug

Intervention Name(s)

placebo oral capsule

Other Intervention Name(s)

Placebo capsule

Intervention Description

placebo oral capsule administered daily for one month.

Primary Outcome Measure Information:

Title

Functional Magnetic Resonance Imaging (fMRI) Changes in Response to Estrogen and Aging - Dorsolateral Pre-frontal Cortex (DLPFC)

Description

Time Frame

baseline to 1 month

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janet E Hall, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Reproductive Endocrine Unit, Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified information will be made available on request to the PI once the primary data analysis has been published.

IPD Sharing Time Frame

From time of publication of initial 2 manuscripts (December 2019) for 5 years

IPD Sharing Access Criteria

Academic investigator with funding for analysis, approval of PI

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Aging and Estrogen on Cortical Function

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