Continuation of The Kronos Early Estrogen Prevention Study (KEEPS) (KEEPS)

Prevention of Alzheimer's Disease in Women: Risks and Benefits of Hormone Therapy -Continuation of: "The Kronos Early Estrogen Prevention Study (KEEPS)"

The purpose of this study is to investigate how blood flow to the brain affects cognition in women who are postmenopausal, and how the use of hormone therapy early in menopause might change brain function. The testing in this study will add to the knowledge about brain aging in women. Researchers will determine if blood flow to the brain, brain structure, and cognition differences among women who took hormones in the past as part of Kronos Early Estrogen Prevention Study (KEEPS; NCT00154180), are currently taking hormones, or never took menopausal hormones.

Study Overview

• Status: Completed
• Conditions: Alzheimer Dementia
• Intervention / Treatment: Diagnostic test: Brain Magnetic Resonance Imaging (MRI); Diagnostic test: F-18 Florbetapir Positron Emission Tomography (PET) Imaging; Diagnostic test: F-18 AV-1451 Positron Emission Tomography (PET) Imaging; Other: Neuropsychological Testing

Detailed Description

This is a continuation of the Kronos Early Estrogen Prevention Study (KEEPS) (KEEPS; NCT00154180), a multicenter double blinded, placebo-controlled, randomized trial funded by the Kronos Longevity Research Institute, Phoenix, AZ to test the hypothesis that hormone therapy started early in menopause (within the "window of opportunity") would slow progression of atherosclerosis as measured by changes in carotid artery intima-medial thickening and coronary arterial calcification.

This study will involve a single follow-up evaluation of brain imaging and cognitive function of women who were randomized to menopausal hormone therapy (mHT) or placebo, approximately 13 years post-randomization and nine years after the end of mHT administration phase in KEEPS (NCT00154180). No interventions are given as part of this study; any current hormonal treatments are by choice and prescribed by the participant's personal physician.

• Study Type: Observational
• Enrollment (Actual): 299
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Banner Health
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States, 10027
      • Columbia University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women that participated in the Kronos Early Estrogen Prevention Study (KEEP; NCT00154180) and completed brain imaging or cognitive testing and indicated that it would be acceptable to contact them for future research opportunities.

Description

Inclusion Criteria:

• Participated in the original KEEPS trial.
• Able to understand study procedures.
• Willing to sign an authorization of consent in order to participate in this study.

Exclusion Criteria:

• Women who have contraindications to MRI or PET for safety reasons, such as an MRI-incompatible implant or claustrophobia.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Menopausal Hormone Therapy (mHT) Group; Women that participated in and completed the KEEPS study (NCT00154180) that were randomized to receive menopausal hormone therapy (mHT) will have a follow up brain Positron Emission Tomography (PET) imaging (F-18 Florbetapir PET or F-18 AV-1451 PET) and cognitive function testing.	Diagnostic test: Brain Magnetic Resonance Imaging (MRI); Performed on a single 3T system and sequences will be acquired in a single sitting with an exam time under 45 minutes.; Diagnostic test: F-18 Florbetapir Positron Emission Tomography (PET) Imaging; After a 50-minute uptake period, the patient will be positioned on the scanner bed with instructions to remain motionless. Injection of 10 mCi of 18F-Florbetapir (target dose 370 MBq, range 296 - 444 MBq) given. A helical CT image will be obtained at 50 minutes after injection of 18F-Florbetapir, followed by a 20-minute PET acquisition consisting of four 5-minute dynamic frames.; Diagnostic test: F-18 AV-1451 Positron Emission Tomography (PET) Imaging; Intravenous bolus injection of approximately 370 MBq (10 mCi) of 18F- AV-1451 (approved under IND 124449). PET/CT image acquisition will include a low dose CT and then a 20-minute PET acquisition starting at 50-60 minutes after injection of 18F-T807 and will be performed as 4, 5-minute frames that will then be summed into one static frame. Serial frames will allow for adjustment in the case of patient motion.; Other: Neuropsychological Testing; A comprehensive battery of standardized neuropsychological tests administered by trained personnel.
Placebo Group; Women that participated in and completed the KEEPS study (NCT00154180) that were randomized to receive placebo treatment will have a follow up brain Positron Emission Tomography (PET) imaging (F-18 Florbetapir PET or F-18 AV-1451 PET) and cognitive function testing.	Diagnostic test: Brain Magnetic Resonance Imaging (MRI); Performed on a single 3T system and sequences will be acquired in a single sitting with an exam time under 45 minutes.; Diagnostic test: F-18 Florbetapir Positron Emission Tomography (PET) Imaging; After a 50-minute uptake period, the patient will be positioned on the scanner bed with instructions to remain motionless. Injection of 10 mCi of 18F-Florbetapir (target dose 370 MBq, range 296 - 444 MBq) given. A helical CT image will be obtained at 50 minutes after injection of 18F-Florbetapir, followed by a 20-minute PET acquisition consisting of four 5-minute dynamic frames.; Diagnostic test: F-18 AV-1451 Positron Emission Tomography (PET) Imaging; Intravenous bolus injection of approximately 370 MBq (10 mCi) of 18F- AV-1451 (approved under IND 124449). PET/CT image acquisition will include a low dose CT and then a 20-minute PET acquisition starting at 50-60 minutes after injection of 18F-T807 and will be performed as 4, 5-minute frames that will then be summed into one static frame. Serial frames will allow for adjustment in the case of patient motion.; Other: Neuropsychological Testing; A comprehensive battery of standardized neuropsychological tests administered by trained personnel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aβ PET SUVR	This measure is derived from a PET imaging study that images the deposition of the amyloid plaques of Alzheimer's disease in the brain	4 years
WMH volume	This measure is derived from an MRI study that images the brain structure. WMH is measured from specific regions of the brain that are vulnerable to cerebrovascular disease related injury.	4 years
Regional cortical thickness	This measure is derived from an MRI study that images the brain structure. The cortical thickness is measured from specific regions of the brain that are vulnerable to Alzheimer's disease related neurodegeneration.	4 years
AV-1451	This measure is derived from a PET imaging study that images the deposition of the tau protein of Alzheimer's disease in the brain	4 years
Global cognitive function	This measurement is derived from multiple neuropsychometric tests that measure various cognitive abilities.	4 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Yale University; Columbia University; National Institute on Aging (NIA); Brigham and Women's Hospital; University of California, San Francisco; Utah State University; Banner Alzheimer's Institute
• Investigators: Principal Investigator: Kejal Kantarci, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2019
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 12-008697; 1RF1AG057547-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study data will be de-identified and transferred to the Mayo Clinic and UW through secure file transfer protocols. Data will be stored at each institution's data center.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No