Clinical trial NCT00115024: EPAT: Estrogen in the Prevention of Atherosclerosis Trial
Official title: Estrogen in the Prevention of Atherosclerosis Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Atherosclerosis
Postmenopause
Keywords: cardiovascular disease
CVD
estrogen
cholesterol
LDL
lipids
postmenopausal
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Mead Johnson Nutrition
First posted: 2005-06-21
Enrollment: 222
Sex: FEMALE
Minimum age (years): 46
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the effects of estrogen replacement therapy (ERT) on the progression of early atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease (CVD).

Detailed description: The primary goal of this randomized, controlled trial is to determine if ERT stabilizes, retards, and/or reverses the progression of atherosclerosis in postmenopausal women. We will further evaluate the association of lipid and non-lipid factors of ERT-mediated reduction in the progression of early atherosclerosis. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery. Blood samples will be used for measuring lipid and non-lipid mediators of ERT.

A total of 222 healthy postmenopausal women 46 to 80 years old without CVD symptoms will be randomized to receive either micronized 17B-estradiol (Estrace) 1mg/day, or a matching placebo tablet daily. All women will be on a low fat/low cholesterol diet, and will receive pravastatin if their LDL cholesterol level exceeds 160 mg/dL. Participants will undergo ultrasonography at baseline and every 6 months throughout the 2 years of randomized treatment. Measurements of lipid and non-lipid biochemical markers will also be done at baseline and every 6 months.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal female (serum estradiol less than 20 pg/ml)
* 46 to 80 years old
* Fasting LDL-C levels 130 to 210 mg/dL
* Triglyceride levels less than 400 mg/dL
* Current non-smoker

Exclusion Criteria:

* Clinical evidence of cardiovascular disease
* HDL-C level less than 30 mg/dL
* Fasting blood glucose greater than 200 mg/dL
* Previous hormonal replacement therapy (non-contraceptive) over 10 years duration and/or current use within 1 month
* Uncontrolled hypertension
* Untreated thyroid disease
* Renal insufficiency
* Clinical evidence of congestive heart failure
* Life threatening disease with prognosis less than 5 years
* Alcohol intake greater than 5 drinks per day (1 drink = 1 1/2 oz distilled spirits, 4 oz wine, or 12 oz beer) or substance abuse (intravenous drug abuse, cocaine use)
* History of estrogen dependent cancer or detected at screening or any other disorder precluding use of ERT
* Hot flashes greater than 5 per day which interfere with daily activity and preclude randomization to placebo.

Primary outcomes:
measure: rate of change of distal common carotid artery (CCA) far wall intima-media thickness (IMT)
Secondary outcomes:
measure: lipid and non-lipid factors
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine
state: California
Study officials:
affiliation: University of Southern California, Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine
name: Howard N. Hodis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, Selzer RH, Liu Cr CR, Liu Ch CH, Azen SP; Estrogen in the Prevention of Atherosclerosis Trial Research Group. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001 Dec 4;135(11):939-53. doi: 10.7326/0003-4819-135-11-200112040-00005.
citation: Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, Hodis HN. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7. doi: 10.1097/01.AOG.0000251518.56369.eb.