Kronos Early Estrogen Prevention Study (KEEPS)

Menopause Clinical Trial

Official title:

Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00154180
• Other study ID #: KLRI-04-1
• Secondary ID: WIRB Protocol #2
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 7, 2005
• Last updated: September 10, 2009
• Start date: September 2005
• Est. completion date: July 2012

Study information

• Verified date: September 2009
• Source: Kronos Longevity Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00623311

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 728
• Est. completion date: July 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 42 Years to 58 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arteriosclerosis
• Menopause

Intervention

Drug:
• Conjugated equine estrogens 0.45 mg/day
Pill, 1 pill taken daily each month for the study duration
• Transdermal estradiol, 50 mcg/day
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
capsule, 1 capsule taken daily for the first 12 days of each month for the study duration
• 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
• 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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Yale University Medical Center	New Haven	Connecticut
United States	Columbia Presbyterian Hospital	New York	New York
United States	Kronos Longevity Research Institute	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington/VA Puget Sound, HCS	Seattle/Tacoma	Washington

Sponsors (9)

Lead Sponsor	Collaborator
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

Country where clinical trial is conducted

United States, 

References & Publications (3)

Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N. KEEPS: The Kronos Early Estrogen Prevention Study. Climacteric. 2005 Mar;8(1):3-12. — View Citation

Harman SM, Brinton EA, Clarkson T, Heward CB, Hecht HS, Karas RH, Judelson DR, Naftolin F. Is the WHI relevant to HRT started in the perimenopause? Endocrine. 2004 Aug;24(3):195-202. — View Citation

Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the estrogen controversy over? Deconstructing the Women's Health Initiative study: a critical evaluation of the evidence. Ann N Y Acad Sci. 2005 Jun;1052:43-56. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change of carotid intimal medial thickness by ultrasound		Measured at screening, 12, 24, 36, and 48 months	No
Secondary	Change in coronary calcium score by X-ray tomography		Meassured at screening and at 48 months	No
Secondary	Plasma lipid profiles		Samples taken at screening , 12, 36, and 48 months	No
Secondary	Blood clotting factors		Samples taken at screening, 12, 36 and 48 months	No
Secondary	Serum inflammatory factors		Samples taken at screening, 12, 36 and 48 months	No
Secondary	Hormone levels		Samples taken at screening, 12, 36 and 48 months	No
Secondary	Cognitive and Affective scores on standard psychometric tests		Testing is conducted at Baseline, 18, 36 and 48 months	No
Secondary	Quality of life		Measured at Baseline, 18, 36 and 48 months	No

External Links

•   Information on hormone treatment and KEEPS rationale
•   Information on sponsoring institution