Aging and Estrogen on Cortical Function

NCT01268046 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2009P-002311R01AG013241
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Memory Loss; Cognitive Changes; Postmenopausal Symptoms

Keywords

aging; postmenopausal women; estrogen; memory

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline to 1 month

Study Arms (4)

Young postmenopausal women - estrogen

EXPERIMENTAL

transdermal estrogen patch OR estradiol oral capsule for 1 month

Drug: Estradiol oral capsule; Drug: transderman estrogen patch

Older postmenopausal women - estrogen

EXPERIMENTAL

transdermal estrogen patch OR estradiol oral capsule for 1 month

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

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

Drug: trasdermal placebo patch; Drug: placebo oral capsule

Interventions

Estradiol oral capsule DRUG

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

Also known as: Micronized Estradiol, Estradiol

Older postmenopausal women - estrogen; Young postmenopausal women - estrogen

transderman estrogen patch DRUG

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

Also known as: Climara, Estraderm, Estrogen patch

Older postmenopausal women - estrogen; Young postmenopausal women - estrogen

trasdermal placebo patch DRUG

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

Also known as: Placebo patch

Older postmenopausal women - placebo; Young postmenopausal women - placebo

placebo oral capsule DRUG

placebo oral capsule administered daily for one month.

Also known as: Placebo capsule

Older postmenopausal women - placebo; Young postmenopausal women - placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Reproductive Endocrine Unit, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Memory Disorders

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Janet Hall, MD
• Organization: Massachusetts General Hospital

janet.hall@nih.gov

617-877-1112

Study Officials

• Janet E Hall, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization was performed by the Research Pharmacy and the investigative team was blinded.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

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

Study Record Dates

• First Submitted: December 28, 2010
• First Posted: December 29, 2010
• Study Start: November 1, 2009
• Primary Completion: December 2, 2013
• Study Completion: December 2, 2013
• Last Updated: August 22, 2018
• Results First Posted: August 22, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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

Locations

US (1)