ELITE: Early Versus Late Intervention Trial With Estradiol

Atherosclerosis Clinical Trial

Official title:

Biologic Response of Menopausal Women to 17B-Estradiol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114517
• Other study ID #: AG0025
• Secondary ID: R01AG024154
• Status: Completed
• Phase: Phase 2
• Start date: July 2004
• Est. completion date: March 5, 2013

Study information

• Verified date: December 2022
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the effects of oral 17B-estradiol (estrogen) on the progression of early (subclinical) atherosclerosis and cognitive decline in healthy postmenopausal women.

Description:

The primary hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of early atherosclerosis if initiated soon after menopause when the vascular endothelium (lining of blood vessels) is relatively healthy versus later when the endothelium has lost its responsiveness to estrogen. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery and cardiac computed tomography (CT) will be used to measure coronary artery calcium and coronary artery lesions. The second hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of cognitive decline if initiated soon after menopause when healthy brain tissue remains responsive to estrogen versus later when brain tissue has lost its responsiveness to estrogen.

A total of 643 (actual; 504 initially proposed) postmenopausal women were randomized according to their number of years since menopause, less than 6 years or 10 years or more, to receive either oral 17B-estradiol 1 mg daily or matching placebo. Women with a uterus will also use vaginal progesterone gel 4% (or placebo gel) the last ten days of each month. The vaginal progesterone will be distributed in a double-blinded fashion along with the randomized treatment so that only women exposed to active treatment will receive active progesterone. As initially proposed, participants will undergo ultrasonography at baseline and every 6 months throughout the 2 to 5 years (average 3 years) of randomized treatment. Participants will also undergo cognitive testing at baseline and after 3 years of randomized treatment. The trial has been extended for an additional 2 to 2.5 years of randomized treatment (overall average randomized treatment of 5 years and range of 2 to 8.5 years). Ultrasonography will continue to be collected every 6 months and upon completion of randomized treatment, participants will undergo cardiac CT for coronary artery calcium and coronary artery lesion measurements. Participants will also undergo a third cognitive testing at the completion of randomized treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 643
• Est. completion date: March 5, 2013
• Est. primary completion date: February 12, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Women with a serum estradiol level 25 pg/ml or less

• No period for 6 months or more

• Postmenopausal less than 6 years, OR 10 years or longer

Exclusion Criteria:

• Clinical signs, symptoms, or personal history of cardiovascular disease

• Women who have had a hysterectomy only and no oophorectomy (since time from menopause cannot be determined)

• Diabetes mellitus or fasting serum glucose 140 mg/dL or greater

• Uncontrolled hypertension (diastolic blood pressure 110 mmHg or greater)

• Thyroid disease (untreated)

• Serum creatinine greater than 2.0 mg/dL

• Plasma triglyceride levels greater than 500 mg/dL

• Life threatening disease with prognosis less than 5 years

• Cirrhosis or liver disease

• History of deep vein thrombosis or pulmonary embolism

• History of breast cancer

• Current hormone replacement therapy (HRT)

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• 17B-estradiol
Oral 17B-estradiol 1 mg daily

Other:
• Placebo
Matching oral 17B-estradiol placebo daily

Locations

Country	Name	City	State
United States	Atherosclerosis Research Unit, University of Southern California	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Henderson VW, St John JA, Hodis HN, McCleary CA, Stanczyk FZ, Shoupe D, Kono N, Dustin L, Allayee H, Mack WJ. Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology. 2016 Aug 16;87(7):699-708. doi: 10.1212/W — View Citation

Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, Li Y, Feng M, Dustin L, Kono N, Stanczyk FZ, Selzer RH, Azen SP; ELITE Research Group. Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol. N Engl J Med. 2016 — View Citation

Hodis HN, Mack WJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, Budoff MJ, Henderson VW. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause. 2015 Apr;22(4):391-401. doi: 10.1097/GME.0000000000000343. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of Subclinical Atherosclerosis	Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (mm per year) in computer image processed B-mode ultrasonograms that were obtained at two baseline examinations (averaged to obtain the baseline CIMT value) and every 6 months during trial follow-up.	Baseline x 2 and then every 6 months up to 6.7 years
Secondary	Change in Neurocognitive Function (Global Cognition)	All neuropsychological test scores at baseline and follow-up assessments were standardized ([raw score - mean score]/standard deviation) using the baseline means and standard deviations from the entire ELITE sample. Each of three cognitive composite scores was calculated at baseline and follow-up assessments as the weighted average of the individual donor standardized test scores, weighted by the inverse correlation among tests.The change from baseline (endpoint minus baseline cognitive outcome) was computed for each of the cognitive scores (verbal memory, global cognition, and executive functions). Since the outcome is not a single test but a weighted average of multiple tests, the range is not standard and not reported. Higher scores mean better outcomes.	Baseline and at 2.5 years and 5 years
Secondary	Coronary Artery Calcium	Number of participants with coronary artery calcium measured by cardiac computed tomography	End of randomized treatment, up to 6.7 years