We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Kronos Early Estrogen Prevention Study (KEEPS)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2009 by Kronos Longevity Research Institute.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00154180
First Posted: September 12, 2005
Last Update Posted: September 14, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Albert Einstein College of Medicine, Inc.
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
  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
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Effects of Estrogen Replacement on Atherosclerosis Progression in Recently Menopausal Women

Resource links provided by NLM:


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 ]

Secondary Outcome Measures:
  • 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 ]

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:
  • Premarin
  • Prometrium
  • Climara
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:
  • 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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   42 Years to 58 Years   (Adult)
Sexes 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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, Inc.
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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Owen CM, Pal L, Mumford SL, Freeman R, Isaac B, McDonald L, Santoro N, Taylor HS, Wolff EF. Effects of hormones on skin wrinkles and rigidity vary by race/ethnicity: four-year follow-up from the ancillary skin study of the Kronos Early Estrogen Prevention Study. Fertil Steril. 2016 Oct;106(5):1170-1175.e3. doi: 10.1016/j.fertnstert.2016.06.023. Epub 2016 Jul 5.
Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, Brinton EA, Cedars MI, Lobo RA, Merriam GR, Neal-Perry G, Santoro NF, Taylor HS, Black DM, Budoff MJ, Hodis HN, Naftolin F, Harman SM, Asthana S. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015 Jun 2;12(6):e1001833; discussion e1001833. doi: 10.1371/journal.pmed.1001833. eCollection 2015 Jun.
Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, Hopkins PN, Lobo RA, Manson JE, Merriam GR, Miller VM, Neal-Perry G, Santoro N, Taylor HS, Vittinghoff E, Yan M, Hodis HN. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014 Aug 19;161(4):249-60. doi: 10.7326/M14-0353.
Dowling NM, Gleason CE, Manson JE, Hodis HN, Miller VM, Brinton EA, Neal-Perry G, Santoro MN, Cedars M, Lobo R, Merriam GR, Wharton W, Naftolin F, Taylor H, Harman SM, Asthana S. Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance. PLoS One. 2013 Jul 17;8(7):e68741. doi: 10.1371/journal.pone.0068741. Print 2013.
Ogorodnikova AD, Khan UI, McGinn AP, Zeb I, Budoff MJ, Harman SM, Miller VM, Brinton EA, Manson JE, Hodis HN, Merriam GR, Cedars MI, Taylor HS, Naftolin F, Lobo RA, Santoro N, Wildman RP. Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study. Obesity (Silver Spring). 2013 Aug;21(8):1726-33. doi: 10.1002/oby.20200. Epub 2013 May 13.
Farr JN, Khosla S, Miyabara Y, Miller VM, Kearns AE. Effects of estrogen with micronized progesterone on cortical and trabecular bone mass and microstructure in recently postmenopausal women. J Clin Endocrinol Metab. 2013 Feb;98(2):E249-57. doi: 10.1210/jc.2012-3406. Epub 2013 Jan 15.
Wolff EF, He Y, Black DM, Brinton EA, Budoff MJ, Cedars MI, Hodis HN, Lobo RA, Manson JE, Merriam GR, Miller VM, Naftolin F, Pal L, Santoro N, Zhang H, Harman SM, Taylor HS. Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS). Fertil Steril. 2013 Apr;99(5):1385-91. doi: 10.1016/j.fertnstert.2012.11.053. Epub 2013 Jan 8.
Huang G, Wang D, Khan UI, Zeb I, Manson JE, Miller V, Hodis HN, Budoff MJ, Merriam GR, Harman MS, Brinton EA, Cedars MI, Su Y, Lobo RA, Naftolin F, Santoro N, Taylor HS, Wildman RP. Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study. Cardiovasc Diabetol. 2012 May 15;11:52. doi: 10.1186/1475-2840-11-52.
Huang G, Wang D, Zeb I, Budoff MJ, Harman SM, Miller V, Brinton EA, El Khoudary SR, Manson JE, Sowers MR, Hodis HN, Merriam GR, Cedars MI, Taylor HS, Naftolin F, Lobo RA, Santoro N, Wildman RP. Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS). Atherosclerosis. 2012 Mar;221(1):198-205. doi: 10.1016/j.atherosclerosis.2011.12.004. Epub 2011 Dec 9.
Henderson VW. Aging, estrogens, and episodic memory in women. Cogn Behav Neurol. 2009 Dec;22(4):205-14. doi: 10.1097/WNN.0b013e3181a74ce7. Review.
Mulvagh SL, Behrenbeck T, Lahr BA, Bailey KR, Zais TG, Araoz PA, Miller VM. Endothelial function and cardiovascular risk stratification in menopausal women. Climacteric. 2010 Feb;13(1):45-54. doi: 10.3109/13697130902943287.

Responsible Party: S. Mitchell Harman, MD, PhD/Director, Kronos Longevity Research Institute
ClinicalTrials.gov Identifier: NCT00154180     History of Changes
Obsolete Identifiers: NCT00623311
Other Study ID Numbers: KLRI-04-1
WIRB Protocol #20040792
First Submitted: September 7, 2005
First Posted: September 12, 2005
Last Update Posted: September 14, 2009
Last Verified: September 2009

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
Estrogens, Conjugated (USP)
Progesterone
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins


To Top