Kronos Early Estrogen Prevention Study (KEEPS)

September 10, 2009 updated by: Kronos Longevity Research Institute

Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women

The study will examine the effects of estrogen and progesterone on the development of atherosclerosis in menopausal women when hormone treatment is initiated within 3 years of the menopausal transition.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The KEEPS is designed to explore the hypothesis that early initiation of hormone therapy, in women who are at the inception of their menopause, will decrease the rate of accumulation of atherosclerotic plaque, indicating a likely delay in the onset of clinical cardiovascular disease. The study is designed as a multicenter, 4 year randomized clinical trial. It will evaluate the effectiveness of of 0.45 mg/day of oral conjugated equine estrogens or 50 mcg/day of transdermal estradiol via skin patch changed weekly (each in combination with cyclic oral, micronized progesterone, 200 mg daily for 12 days per month), versus placebo in preventing progression of carotid intimal medial thickness by sonogram and the accrual of coronary calcium in women aged 42-58 who are within 36 months of their final menstrual period at initiation of treatment. A number of secondary endpoints including biochemical and genetic risk factors for cardiovascular and thrombotic disease, and effects on cognition will also be studied. The study will enroll a total of 720 women in 2005-6, with an anticipated completion of the trial in 2010.

Study Type

Interventional

Enrollment (Anticipated)

728

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016-3452
        • Kronos Longevity Research Institute
    • California
      • San Francisco, California, United States, 94115
        • University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine
      • New York, New York, United States, 10032
        • Columbia Presbyterian Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah
    • Washington
      • Seattle/Tacoma, Washington, United States, 98493
        • University of Washington/VA Puget Sound, HCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

42 years to 58 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • menses absent for at least 6 months and no more than 36 months
  • good general health
  • plasma FSH level greater than or equal to 35 mIU/ml
  • estradiol levels < 40 pg/ml
  • normal mammogram within 1 year of randomization

Exclusion Criteria:

  • use of hormone replacement or supplement within 3 months of randomization
  • endometrial thickness >5 mm by vaginal ultrasound
  • in utero exposure to diethylstilbestrol (DES)
  • current smoking > 10 cigarettes/day
  • obesity-body mass index > 35
  • history of clinical cardiovascular disease
  • history of cerebrovascular disease
  • history of thromboembolic disease
  • coronary calcium score ≥ 50 units
  • dyslipidemia-LDL cholesterol >190 mg/dl
  • hypertriglyceridemia-triglycerides >400 mg/dl
  • lipid lowering medication (statin, fibrate,or > 500 mg/day of niacin)
  • nut allergy (Prometrium includes peanut oil)
  • uncontrolled hypertension-systolic BP >150 and/or diastolic BP > 95
  • hysterectomy
  • history of, or prevalent, chronic diseases including any cancer (other than basal cell skin cancers), renal failure, cirrhosis, diabetes mellitus, and endocrinopathies other than adequately treated thyroid disease
  • known HIV infection and/or medications for HIV infection
  • results of any safety laboratory test chemistries, (TSH, CBC, U/A) more than 20% abnormal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Arm 1
CEE 0.45 mg w/ Prometrium 200 mg patch 0.05 mg w/ Prometrium 200 mg
Drug: Conjugated equine estrogens 0.45 mg/day
Pill, 1 pill taken daily each month for the study duration
Other Names:
  • Premarin or placebo
Drug: Transdermal estradiol, 50 mcg/day
Patch; 1 patch is applied to the skin weekly. Patch site is rotated on a weekly basis.
Other Names:
  • Climara 50 mcg/day or placebo
Drug: Micronized progesterone, 200 mg/day x 12 d/month
capsule, 1 capsule taken daily for the first 12 days of each month for the study duration
Other Names:
  • Prometrium or placebo
Drug: CEE, progesterone, transdermal patch or the placebo
CEE 0.45 mg 1 PO QD or placebo equivalent Prometrium 200 mg 1 PO qHS for first 12 dasy of each month or placebo equivalent transdermal patch 0.05 mg use 1 patch per week or placebo equivalent
Other Names:
  • Climara
  • Prometrium
  • Premarin
PLACEBO_COMPARATOR: Arm 2
Placebo patch, placebo CEE, placebo Prometrium
Drug: CEE, progesterone, transdermal patch or the placebo
CEE 0.45 mg 1 PO QD or placebo equivalent Prometrium 200 mg 1 PO qHS for first 12 dasy of each month or placebo equivalent transdermal patch 0.05 mg use 1 patch per week or placebo equivalent
Other Names:
  • Climara
  • Prometrium
  • Premarin
Drug: CEE , progesterone, estradiol patch or placebo for each
CEE 0.45mg 1 PO QD Progesterone 200 mg 1 PO HS first 12 days of the month estradiol patch use 1 per week
Other Names:
  • Prometrium
  • Premarin
  • Climara Patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of change of carotid intimal medial thickness by ultrasound
Time Frame: Measured at screening, 12, 24, 36, and 48 months
Measured at screening, 12, 24, 36, and 48 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in coronary calcium score by X-ray tomography
Time Frame: Meassured at screening and at 48 months
Meassured at screening and at 48 months
Plasma lipid profiles
Time Frame: Samples taken at screening , 12, 36, and 48 months
Samples taken at screening , 12, 36, and 48 months
Blood clotting factors
Time Frame: Samples taken at screening, 12, 36 and 48 months
Samples taken at screening, 12, 36 and 48 months
Serum inflammatory factors
Time Frame: Samples taken at screening, 12, 36 and 48 months
Samples taken at screening, 12, 36 and 48 months
Hormone levels
Time Frame: Samples taken at screening, 12, 36 and 48 months
Samples taken at screening, 12, 36 and 48 months
Cognitive and Affective scores on standard psychometric tests
Time Frame: Testing is conducted at Baseline, 18, 36 and 48 months
Testing is conducted at Baseline, 18, 36 and 48 months
Quality of life
Time Frame: Measured at Baseline, 18, 36 and 48 months
Measured at Baseline, 18, 36 and 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kronos Longevity Research Institute

Collaborators

Mayo Clinic
Albert Einstein College of Medicine
Yale University
Columbia University
Brigham and Women's Hospital
University of Washington
University of California, San Francisco
University of Utah

Investigators

  • Study Director: S Mitchell Harman, MD, PhD, Kronos Longevity Research Institute
  • Study Director: Frederick Naftolin, MD, PhD, Kronos Longevity Research Institute
  • Principal Investigator: Michael Mendelsohn, MD, Tufts Medical Center
  • Principal Investigator: Howard Hodis, MD, University of Southern California
  • Principal Investigator: Matthew Budoff, MD, University of California, Los Angeles
  • Principal Investigator: Dennis M Black, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (ANTICIPATED)

May 1, 2012

Study Completion (ANTICIPATED)

July 1, 2012

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (ESTIMATE)

September 12, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

September 14, 2009

Last Update Submitted That Met QC Criteria

September 10, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KLRI-04-1
  • WIRB Protocol #20040792

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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