Overview

This trial is active, not recruiting.

Conditions menopause, arteriosclerosis
Treatments conjugated equine estrogens 0.45 mg/day, transdermal estradiol, 50 mcg/day, micronized progesterone, 200 mg/day x 12 d/month, cee , progesterone, estradiol patch or placebo for each, cee, progesterone, transdermal patch or the placebo
Phase phase 4
Sponsor Kronos Longevity Research Institute
Collaborator Albert Einstein College of Medicine of Yeshiva University
Start date September 2005
End date May 2012
Trial size 728 participants
Trial identifier NCT00154180, KLRI-04-1, WIRB Protocol #20040792

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Active Comparator)
CEE 0.45 mg w/ Prometrium 200 mg patch 0.05 mg w/ Prometrium 200 mg
conjugated equine estrogens 0.45 mg/day Premarin or placebo
Pill, 1 pill taken daily each month for the study duration
transdermal estradiol, 50 mcg/day Climara 50 mcg/day or placebo
Patch; 1 patch is applied to the skin weekly. Patch site is rotated on a weekly basis.
micronized progesterone, 200 mg/day x 12 d/month Prometrium or placebo
capsule, 1 capsule taken daily for the first 12 days of each month for the study duration
cee, progesterone, transdermal patch or the placebo Premarin
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
(Placebo Comparator)
Placebo patch, placebo CEE, placebo Prometrium
cee , progesterone, estradiol patch or placebo for each Premarin
CEE 0.45mg 1 PO QD Progesterone 200 mg 1 PO HS first 12 days of the month estradiol patch use 1 per week
cee, progesterone, transdermal patch or the placebo Premarin
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

Primary Outcomes

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

Secondary Outcomes

Measure
Change in coronary calcium score by X-ray tomography
time frame: Meassured at screening and at 48 months
Plasma lipid profiles
time frame: Samples taken at screening , 12, 36, and 48 months
Blood clotting factors
time frame: Samples taken at screening, 12, 36 and 48 months
Serum inflammatory factors
time frame: Samples taken at screening, 12, 36 and 48 months
Hormone levels
time frame: 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
Quality of life
time frame: Measured at Baseline, 18, 36 and 48 months

Eligibility Criteria

Female participants from 42 years up to 58 years old.

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

Additional Information

Official title Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women
Principal investigator Michael Mendelsohn, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2009.
Information provided to ClinicalTrials.gov by Kronos Longevity Research Institute.