Kronos Early Estrogen Prevention Study (KEEPS)
The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Kronos Longevity Research Institute.
Recruitment status was Active, not recruiting
Recruitment status was Active, not recruiting
Sponsor:
Kronos Longevity Research Institute
Collaborators:
Albert Einstein College of Medicine of Yeshiva University
Brigham and Women's Hospital
Columbia University
Mayo Clinic
University of California, San Francisco
University of Utah
University of Washington
Yale University
Information provided by:
Kronos Longevity Research Institute
ClinicalTrials.gov Identifier:
NCT00154180
First received: September 7, 2005
Last updated: September 10, 2009
Last verified: September 2009
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Purpose
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 Drug: CEE , progesterone, estradiol patch or placebo for each Drug: CEE, progesterone, transdermal patch or the placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention |
| Official Title: | Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women |
Resource links provided by NLM:
Drug Information available for:
Estradiol
Progesterone
Estradiol cypionate
Estradiol valerate
Estradiol acetate
Estrogens, conjugated
Estradiol hemihydrate
U.S. FDA Resources
Further study details as provided by Kronos Longevity Research Institute:
Primary Outcome Measures:
- Rate of change of carotid intimal medial thickness by ultrasound [ Time Frame: Measured at screening, 12, 24, 36, and 48 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Change in coronary calcium score by X-ray tomography [ Time Frame: Meassured at screening and at 48 months ] [ Designated as safety issue: No ]
- Plasma lipid profiles [ Time Frame: Samples taken at screening , 12, 36, and 48 months ] [ Designated as safety issue: No ]
- Blood clotting factors [ Time Frame: Samples taken at screening, 12, 36 and 48 months ] [ Designated as safety issue: No ]
- Serum inflammatory factors [ Time Frame: Samples taken at screening, 12, 36 and 48 months ] [ Designated as safety issue: No ]
- Hormone levels [ Time Frame: Samples taken at screening, 12, 36 and 48 months ] [ Designated as safety issue: No ]
- Cognitive and Affective scores on standard psychometric tests [ Time Frame: Testing is conducted at Baseline, 18, 36 and 48 months ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: Measured at Baseline, 18, 36 and 48 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 728 |
| Study Start Date: | September 2005 |
| Estimated Study Completion Date: | July 2012 |
| Estimated Primary Completion Date: | May 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Name: 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 Name: 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 Name: 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:
|
|
Placebo Comparator: Arm 2
Placebo patch, placebo CEE, placebo Prometrium
|
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:
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:
|
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.
Eligibility| Ages Eligible for Study: | 42 Years to 58 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | Yes |
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 < 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00154180
Locations
| United States, Arizona | |
| Kronos Longevity Research Institute | |
| Phoenix, Arizona, United States, 85016-3452 | |
| United States, California | |
| University of California, San Francisco | |
| San Francisco, California, United States, 94115 | |
| United States, Connecticut | |
| Yale University Medical Center | |
| New Haven, Connecticut, United States, 06519 | |
| United States, Massachusetts | |
| Brigham and Women's Hospital | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New York | |
| Albert Einstein College of Medicine | |
| Bronx, New York, United States, 10461 | |
| Columbia Presbyterian Hospital | |
| New York, New York, United States, 10032 | |
| United States, Utah | |
| University of Utah | |
| Salt Lake City, Utah, United States, 84108 | |
| United States, Washington | |
| University of Washington/VA Puget Sound, HCS | |
| Seattle/Tacoma, Washington, United States, 98493 | |
Sponsors and Collaborators
Kronos Longevity Research Institute
Albert Einstein College of Medicine of Yeshiva University
Brigham and Women's Hospital
Columbia University
Mayo Clinic
University of California, San Francisco
University of Utah
University of Washington
Yale University
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: | Sanjay Asthana, MD | University of Wisconsin, Madison |
| Principal Investigator: | Dennis M Black, PhD | University of California, San Francisco |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | S. Mitchell Harman, MD, PhD/Director, Kronos Longevity Research Institute |
| ClinicalTrials.gov Identifier: | NCT00154180 History of Changes |
| Other Study ID Numbers: | KLRI-04-1, WIRB Protocol #20040792 |
| Study First Received: | September 7, 2005 |
| Last Updated: | September 10, 2009 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Kronos Longevity Research Institute:
|
Perimenopause Coronary Disease Estrogen Replacement Therapy Hormone Replacement Therapy |
Additional relevant MeSH terms:
|
Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Cardiovascular Diseases Estradiol Polyestradiol phosphate Estrogens, Conjugated (USP) Estrogens Progesterone Estradiol valerate Estradiol 3-benzoate |
Estradiol 17 beta-cypionate Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Contraceptive Agents Reproductive Control Agents Therapeutic Uses Contraceptive Agents, Female Progestins |
ClinicalTrials.gov processed this record on May 19, 2013