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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03718494
Recruitment Status : Enrolling by invitation
First Posted : October 24, 2018
Last Update Posted : September 16, 2021
Sponsor:
Collaborators:
Columbia University
Yale University
Utah State University
Brigham and Women's Hospital
Banner Alzheimer's Institute
University of California, San Francisco
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Kejal Kantarci, Mayo Clinic

Brief Summary:
To assess effects of menopausal hormone therapy and normal aging on cognitive performance and imaging markers of brain structure in women approximately thirteen years after enrolling in the KEEPS trial. KEEPS participants were randomized to oral or transdermal estrogen treatments or placebo within three years of menopause. This is a follow up study of these women approximately thirteen years after randomization (9 years after study completion.) No treatments are given as part of this study; any current hormonal treatments are by choice and prescribed by the participant's personal physician.

Condition or disease Intervention/treatment Phase
Alzheimer Dementia Combination Product: F-18 AV-1451 PET Combination Product: F-18 Florbetapir Phase 4

Detailed Description:

The objectives are to assess the long-term risks and benefits of menopausal hormone therapy (mHT) on Alzheimer's disease (AD) pathophysiology, cerebrovascular, cognitive, and mood health in women treated with transdermal 17β-estradiol (tE2) or oCEE compared to placebo within three years of menopause, which is considered to be the "critical window" for mHT.

The Primary Objective is to determine the differences in Alzheimer's Disease biomarkers , cerebrovascular lesion load and brain structure in postmenopausal women who were treated with one of two mHTs vs. placebo after 13 years post-randomization and 9 years after the end of mHT administration phase.

This project is proposed as a continuation to the Kronos Early Estrogen Prevention Study (KEEPS), a nationwide, multi-center, randomized blinded study of mHT in recently menopausal women.

The current investigation will include assessments conducted within a six-week interval over 2- 3 visits, Participants will be on study for up to 3 months while completing medical assessment, questionnaires, blood work, neurocognitive studies, ECG, brain MRI, brain PET.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 688 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a phase 4 intervention in a cohort of post menopausal women.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Prevention of Alzheimer's Disease in Women: Risks and Benefits of Hormone Therapy -Continuation of: "The Kronos Early Estrogen Prevention Study (KEEPS)" Mayo Clinic IRB#2241-04-00
Actual Study Start Date : May 22, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Follow up
Subjects will receive F-18 Florbetapir PET
Combination Product: F-18 Florbetapir
Each participant will be injected with 10 mCi of 18F-Florbetapir (target dose 370 MBq, range 296 - 444 MBq). After a 25-minute uptake period, the patient will be positioned on the scanner bed with instructions to remain motionless. A helical CT image will be obtained at 50 minutes after injection of 18F-Florbetapir, followed by a 10-minute PET acquisition consisting of two 5-minute dynamic frames.

Experimental: Follow up - Mayo Clinic Sites only
Subjects will receive F-18 AV-1451 PET and F-18 Florbetapir PET
Combination Product: F-18 AV-1451 PET
Participants will receive an intravenous bolus injection of approximately 370 MBq (10 mCi) of 18F- AV-1451. PET/CT image acquisition will include a low dose CT and then a 20-minute PET acquisition starting at 80 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.

Combination Product: F-18 Florbetapir
Each participant will be injected with 10 mCi of 18F-Florbetapir (target dose 370 MBq, range 296 - 444 MBq). After a 25-minute uptake period, the patient will be positioned on the scanner bed with instructions to remain motionless. A helical CT image will be obtained at 50 minutes after injection of 18F-Florbetapir, followed by a 10-minute PET acquisition consisting of two 5-minute dynamic frames.




Primary Outcome Measures :
  1. Aβ PET SUVR [ Time Frame: 4 years ]
    This measure is derived from a PET imaging study that images the deposition of the amyloid plaques of Alzheimer's disease in the brain

  2. WMH volume [ Time Frame: 4 years ]
    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.

  3. Regional cortical thickness [ Time Frame: 4 years ]
    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. AV-1451 [ Time Frame: 4 years ]
    This measure is derived from a PET imaging study that images the deposition of the tau protein of Alzheimer's disease in the brain

  5. Global cognitive function [ Time Frame: 4 years ]
    This measurement is derived from multiple neuropsychometric tests that measure various cognitive abilities.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   This is a continuation study. Only women who participated in the previous menopausal hormone therapy trial are eligible for enrollment.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Participants must meet all of the following inclusion criteria in order to participate in this study:

  • completed the KEEPS trial and underwent previous brain imaging and cognitive testing
  • able to understand study procedures
  • willing to sign an authorization of consent in order to participate in this study.

Exclusion Criteria:

Exclusion Criteria for Cognitive Testing:

  • Current use of medications that would affect cognitive testing, including: opioids, benzodiazepines, or antipsychotics.
  • Evidence of structural brain abnormalities

Exclusion Criteria for MRI and PET imaging:

  • Women who have contraindications to MRI or PET for safety reasons, such as an MRI-incompatible implant or claustrophobia
  • Women with a ECG diagnosis of torsades de pointes which is a rare cardiac arrhythmia or additional risk factors for torsades de pointes such as women with a prolonged QT interval (as demonstrated by ECG test) or taking drugs that prolong QT interval cannot participate in the Tau-PET scans.

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): NCT03718494


Locations
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United States, Arizona
Banner Health
Phoenix, Arizona, United States, 85032
United States, California
University of California San Francisco
San Francisco, California, United States, 94158
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, New York
Columbia University
New York, New York, United States, 10027
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Mayo Clinic
Columbia University
Yale University
Utah State University
Brigham and Women's Hospital
Banner Alzheimer's Institute
University of California, San Francisco
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Kejal Kantarci, M.D. Cons-Neuroradiology
Additional Information:
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Responsible Party: Kejal Kantarci, Professor of Radiology, Cons-Research Neuroradiology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03718494    
Other Study ID Numbers: 12-008697
1RF1AG057547-01 ( U.S. NIH Grant/Contract )
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Tauopathies
Neurodegenerative Diseases