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.

Condition	Intervention	Phase
Menopause Arteriosclerosis	Drug: Conjugated equine estrogens 0.45 mg/day  Drug: Transdermal estradiol, 50 mcg/day  Drug: Micronized progesterone, 200 mg/day x 12 d/month	Phase IV

Further Study Details: 

Primary Outcomes: Rate of change of carotid intimal medial thickness by ultrasound
Secondary Outcomes: Change in coronary calcium score by X-ray tomography; Plasma lipid profiles; Blood clotting factors; Serum inflammatory factors; Hormone levels; Cognitive and Affective scores on standard psychometric tests; Quality of life
Expected Total Enrollment:  720

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 0.45 mg of oral conjugated equine estrogens or 50 mcg weekly transdermal estradiol (both in combination with cyclic oral, micronized progesterone, 200mg for 12 days each 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.

Ages Eligible for Study:  42 Years   -   58 Years,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

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 < 25 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00154180

Patricia Crenshaw, BA      (866) 878-1221    info@kronosinstitute.org
Mary Barksdale, CNM, CCRP      (602) 778-7487 

California
      University of California, San Francisco, San Francisco,  California,  94115,  United States; Recruiting
Connecticut
      Yale University, New Haven,  Connecticut,  06520,  United States; Recruiting
Massachusetts
      Brigham and Women''''s Hospital, Boston,  Massachusetts,  02215,  United States; Recruiting
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States; Recruiting
New York
      Columbia Presbyterian Hospital, New York,  New York,  10032,  United States; Recruiting
      Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States; Recruiting
Utah
      University of Utah, Salt Lake City,  Utah,  84108,  United States; Recruiting
Washington
      University of Washington, Tacoma,  Washington,  98493,  United States; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  KLRI-04-1; WIRB Protocol #20040792
Last Updated:  September 9, 2005
Record first received:  September 7, 2005
ClinicalTrials.gov Identifier:  NCT00154180
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-13