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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
Sponsor:
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

September 7, 2005
September 10, 2009
September 2005
May 2012   (final data collection date for primary outcome measure)
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 ]
Rate of change of carotid intimal medial thickness by ultrasound
Complete list of historical versions of study NCT00154180 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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
Not Provided
Not Provided
 
Kronos Early Estrogen Prevention Study (KEEPS)
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Menopause
  • Arteriosclerosis
  • 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, 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:
    • Premarin
    • Prometrium
    • Climara Patch
  • 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:
    • Premarin
    • Prometrium
    • Climara
  • Active Comparator: Arm 1
    CEE 0.45 mg w/ Prometrium 200 mg patch 0.05 mg w/ Prometrium 200 mg
    Interventions:
    • 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, transdermal patch or the placebo
  • Placebo Comparator: Arm 2
    Placebo patch, placebo CEE, placebo Prometrium
    Interventions:
    • Drug: CEE , progesterone, estradiol patch or placebo for each
    • Drug: CEE, progesterone, transdermal patch or the placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
728
July 2012
May 2012   (final data collection date for primary outcome measure)

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
Female
42 Years to 58 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00154180
KLRI-04-1, WIRB Protocol #20040792
Yes
S. Mitchell Harman, MD, PhD/Director, Kronos Longevity Research Institute
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
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
Kronos Longevity Research Institute
September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP