Trial record 1 of 1 for: Early Versus Late Intervention Trial With Estradiol (ELITE)

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ELITE: Early Versus Late Intervention Trial With Estradiol

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ClinicalTrials.gov Identifier: NCT00114517

Recruitment Status : Completed

First Posted : June 16, 2005

Results First Posted : June 8, 2017

Last Update Posted : June 8, 2017

Sponsor:

Collaborator:

National Institute on Aging (NIA)

Information provided by (Responsible Party):

Howard Hodis, University of Southern California

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition	Atherosclerosis
Interventions	Drug: Oral 17B-estradiol Drug: Placebo
Enrollment	643

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Early Postmenopause 17B-estradiol	Early Postmenopause Placebo	Late Postmenopause 17B-estradiol	Late Postmenopause Placebo
Arm/Group Description	Early postmenopause, <6 years-since...	Early postmenopause <6 years-since-...	Late postmenopause >10 years-since-...	Late postmenopause >10 years-since-...
Arm/Group Description	Early postmenopause, <6 years-since-menopause oral 17B-estradiol 1 mg daily	Early postmenopause <6 years-since-menopause	Late postmenopause >10 years-since-menopause oral 17B-estradiol 1 mg daily	Late postmenopause >10 years-since-menopause
Period Title: Overall Study
Started	137	134	186	186
Completed	125	123	172	176
Not Completed	12	11	14	10

Baseline Characteristics

Arm/Group Title		Early Postmenopause 17B-estradiol	Early Postmenopause Placebo	Late Postmenopause 17B-estradiol	Late Postmenopause Placebo	Total
Arm/Group Description		[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]	Total of all reporting groups
Arm/Group Description		[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]	Total of all reporting groups
Overall Number of Baseline Participants		125	123	172	176	596
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	125 participants	123 participants	172 participants	176 participants	596 participants
		55.4 (53.2 to 57.9)	55.4 (52.5 to 57.8)	64.3 (60.5 to 68.6)	63.0 (59.9 to 67.0)	60.0 (55.5 to 64.8)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	125 participants	123 participants	172 participants	176 participants	596 participants
	Female	125 100.0%	123 100.0%	172 100.0%	176 100.0%	596 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	125 participants	123 participants	172 participants	176 participants	596 participants
White, non-hispanic		88 70.4%	73 59.3%	127 73.8%	127 72.2%	415 69.6%
Black, non-hispanic		7 5.6%	14 11.4%	17 9.9%	14 8.0%	52 8.7%
Hispanic		16 12.8%	20 16.3%	20 11.6%	23 13.1%	79 13.3%
Asian		14 11.2%	16 13.0%	8 4.7%	12 6.8%	50 8.4%

Outcome Measures

1.Primary Outcome


Title	Rate of Change of Distal Common Carotid Artery (CCA) Far Wall Intima-media Thickness (IMT)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Twice at baseline and then every 6 months on trial

Outcome Measure Data

Analysis Population Description

Early postmenopause group (<6 years since menopause) at baseline and late postmenopause group (>10 years since menopause) at baseline.


Arm/Group Title	17B-estradiol	Placebo
Arm/Group Description:	Oral 17B-estradiol 1 mg daily ...	Matched placebo oral 17B-estradiol ...
Arm/Group Description:	Oral 17B-estradiol 1 mg daily Oral 17B-estradiol: Oral 17B-estradiol 1 mg daily	Matched placebo oral 17B-estradiol daily Placebo: Matched placebo oral 17B-estradiol
Overall Number of Participants Analyzed	297	299
Mean (95% Confidence Interval) Unit of Measure: mm per year
Early postmenopause group	0.0044 (0.0026 to 0.0061)	0.0078 (0.0060 to 0.0096)
Late postmenopause group	0.0100 (0.0085 to 0.0115)	0.0088 (0.0073 to 0.0103)

2.Secondary Outcome


Title	Change in Neurocognitive Function (Global Cognition)
Description	All neuropsychological test scores at baseline and follow-up assessmen...
Description	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.
Time Frame	Baseline and at 2.5 years and 5 years

Outcome Measure Data

Analysis Population Description

Early postmenopause group (<6 years since menopause) at baseline and late postmenopause group (>10 years since menopause) at baseline. Sample size represents the number of participants with analyzable data collected at baseline, 2.5 years and 5.0 years.


Arm/Group Title	17B-estradiol	Placebo
Arm/Group Description:	Oral 17B-estradiol 1 mg daily ...	Matched placebo oral 17B-estradiol ...
Arm/Group Description:	Oral 17B-estradiol 1 mg daily Oral 17B-estradiol: Oral 17B-estradiol 1 mg daily	Matched placebo oral 17B-estradiol daily Placebo: Matched placebo oral 17B-estradiol
Overall Number of Participants Analyzed	284	283
Mean (95% Confidence Interval) Unit of Measure: units on a scale
Early postmenopause group	0.42 (0.11 to 0.73)	0.40 (-0.07 to 0.72)
Late postmenopause group	0.29 (0.14 to 0.44)	0.36 (0.20 to 0.53)

3.Secondary Outcome


Title	Number of Participants With Coronary Artery Calcium Measured by Cardiac Computed Tomography
Description	measurement of coronary artery calcium at end of study
Description	measurement of coronary artery calcium at end of study
Time Frame	End of randomized treatment

Outcome Measure Data

Analysis Population Description

CAC data was obtained in 380 participants. Participants who were not taking the study agents at the last follow-up visit, who had adherence to the study regimen that was lower than 80% or who had a CAC scan more than 6 months after the final study visit were not included in the analysis.


Arm/Group Title	17B-estradiol	Placebo
Arm/Group Description:	Oral 17B-estradiol 1 mg daily ...	Matched placebo oral 17B-estradiol ...
Arm/Group Description:	Oral 17B-estradiol 1 mg daily Oral 17B-estradiol: Oral 17B-estradiol 1 mg daily	Matched placebo oral 17B-estradiol daily Placebo: Matched placebo oral 17B-estradiol
Overall Number of Participants Analyzed	188	192
Measure Type: Count of Participants Unit of Measure: Participants
Early postmenopause group	34 18.1%	24 12.5%
Late postmenopause gorup	57 30.3%	65 33.9%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Adverse events collected per intervention

Arm/Group Title	17B-estradiol		Placebo
Arm/Group Description	Oral 17B-estradiol 1 mg daily ...		Matched placebo oral 17B-estradiol ...
Arm/Group Description	Oral 17B-estradiol 1 mg daily Oral 17B-estradiol: Oral 17B-estradiol 1 mg daily		Matched placebo oral 17B-estradiol daily Placebo: Matched placebo oral 17B-estradiol
All-Cause Mortality
	17B-estradiol		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/323 (0.31%)		1/320 (0.31%)
Serious Adverse Events Serious Adverse Events
	17B-estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/323 (13.31%)		45/320 (14.06%)
Blood and lymphatic system disorders
aplastic anemia ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
Cardiac disorders
unstable angina ^†	2/323 (0.62%)	2	0/320 (0.00%)	0
atrial fibrillation ^†	1/323 (0.31%)	1	1/320 (0.31%)	1
pleuropericarditis ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
myocardial infarction ^†	1/323 (0.31%)	1	3/320 (0.94%)	3
Ear and labyrinth disorders
veritgo ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
Gastrointestinal disorders
ischemic colitis ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
gastroesophageal reflux disease ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
illeitis ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
gastrointestinal hemorrhage ^†	1/323 (0.31%)	1	1/320 (0.31%)	1
pancreatitis ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
ulcerative colitis ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
General disorders
death ^†	1/323 (0.31%)	1	1/320 (0.31%)	1
non-cardiac chest pain ^†	2/323 (0.62%)	2	1/320 (0.31%)	1
Immune system disorders
drug hypersensitivity ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
Infections and infestations
cellulitis ^†	0/323 (0.00%)	0	2/320 (0.63%)	2
lobar pneumonia ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
pelvic abscess ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
pneumonia ^†	1/323 (0.31%)	1	1/320 (0.31%)	1
Injury, poisoning and procedural complications
cervical vertebral fracture ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
femoral neck fracture ^†	1/323 (0.31%)	1	3/320 (0.94%)	3
foot fracture ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
fracture ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
Musculoskeletal and connective tissue disorders
systemic lupus erythematosus ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
breast cancer ^†	5/323 (1.55%)	5	4/320 (1.25%)	4
breast cancer in situ ^†	5/323 (1.55%)	5	4/320 (1.25%)	4
colon adenoma ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
colorectal cancer ^†	3/323 (0.93%)	3	2/320 (0.63%)	2
gastric cancer ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
glioblastoma ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
malignant peritoneal neoplasm ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
mycosis fungoides ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
ovarian epithelial cancer ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
pancreatic carcinoma ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
polycythemia vera ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
uterine cancer ^†	2/323 (0.62%)	2	1/320 (0.31%)	1
Nervous system disorders
amnesia ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
dizziness ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
syncope ^†	1/323 (0.31%)	1	1/320 (0.31%)	1
transient ischemic attack ^†	1/323 (0.31%)	1	2/320 (0.63%)	2
Psychiatric disorders
Suicide ideation ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
psychotic disorder ^†	1/323 (0.31%)	1	0/320 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
pulmonary embolism ^†	2/323 (0.62%)	2	0/320 (0.00%)	0
Surgical and medical procedures
spinal laminectomy ^†	0/323 (0.00%)	0	1/320 (0.31%)	1
Vascular disorders
deep vein thrombosis ^†	1/323 (0.31%)	1	2/320 (0.63%)	2
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	17B-estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	216/323 (66.87%)		226/320 (70.63%)
General disorders
chest discomfort ^†	23/323 (7.12%)	23	22/320 (6.88%)	22
non-cardiac chest pain ^†	18/323 (5.57%)	18	12/320 (3.75%)	12
Immune system disorders
drug hypersensitivity ^†	26/323 (8.05%)	26	25/320 (7.81%)	25
Infections and infestations
bronchitis ^†	19/323 (5.88%)	19	22/320 (6.88%)	22
influenza ^†	44/323 (13.62%)	44	52/320 (16.25%)	52
sinusitis ^†	24/323 (7.43%)	24	24/320 (7.50%)	24
urinary tract infection ^†	63/323 (19.50%)	63	64/320 (20.00%)	64
Injury, poisoning and procedural complications
contusion ^†	17/323 (5.26%)	17	12/320 (3.75%)	12
fall ^†	37/323 (11.46%)	37	36/320 (11.25%)	36
road traffic accident ^†	19/323 (5.88%)	19	13/320 (4.06%)	13
Musculoskeletal and connective tissue disorders
arthralgia ^†	47/323 (14.55%)	47	53/320 (16.56%)	53
back pain ^†	35/323 (10.84%)	35	32/320 (10.00%)	32
pain in extremity ^†	10/323 (3.10%)	10	18/320 (5.63%)	18
Psychiatric disorders
depression ^†	17/323 (5.26%)	17	20/320 (6.25%)	20
Reproductive system and breast disorders
cervical dysplasia ^†	48/323 (14.86%)	48	42/320 (13.13%)	42
vaginal discharge ^†	17/323 (5.26%)	17	8/320 (2.50%)	8
vulvovaginal pruritis ^†	19/323 (5.88%)	19	11/320 (3.44%)	11
Respiratory, thoracic and mediastinal disorders
cough ^†	25/323 (7.74%)	25	19/320 (5.94%)	19
Skin and subcutaneous tissue disorders
rash ^†	16/323 (4.95%)	16	22/320 (6.88%)	22
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Howard N. Hodis, M.D., Director, Atherosclerosis Research Unit
Organization:	University of Southern California
Phone:	323 442 1478
EMail:	athero@usc.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lin F, Pa J, Karim R, Hodis HN, Han SD, Henderson VW, St John JA, Mack WJ. Subclinical carotid artery atherosclerosis and cognitive function in older adults. Alzheimers Res Ther. 2022 May 7;14(1):63. doi: 10.1186/s13195-022-00997-7.

Sriprasert I, Mert M, Mack WJ, Hodis HN, Shoupe D. Use of oral estradiol plus vaginal progesterone in healthy postmenopausal women. Maturitas. 2021 Dec;154:13-19. doi: 10.1016/j.maturitas.2021.09.002. Epub 2021 Sep 5.

Sriprasert I, Kono N, Karim R, Hodis HN, Stanczyk FZ, Shoupe D, Mack WJ. Factors Associated With Serum Estradiol Levels Among Postmenopausal Women Using Hormone Therapy. Obstet Gynecol. 2020 Oct;136(4):675-684. doi: 10.1097/AOG.0000000000004006.

Sriprasert I, Mack WJ, Hodis HN, Allayee H, Brinton RD, Karim R. Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women. Am J Cardiol. 2019 Oct 1;124(7):1031-1037. doi: 10.1016/j.amjcard.2019.06.022. Epub 2019 Jul 15.

Sriprasert I, Hodis HN, Karim R, Stanczyk FZ, Shoupe D, Henderson VW, Mack WJ. Differential Effect of Plasma Estradiol on Subclinical Atherosclerosis Progression in Early vs Late Postmenopause. J Clin Endocrinol Metab. 2019 Feb 1;104(2):293-300. doi: 10.1210/jc.2018-01600.

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 Mar 31;374(13):1221-31. doi: 10.1056/NEJMoa1505241.

Karim R, Stanczyk FZ, Brinton RD, Rettberg J, Hodis HN, Mack WJ. Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J Clin Endocrinol Metab. 2015 Feb;100(2):508-15. doi: 10.1210/jc.2014-1839. Epub 2014 Nov 18.

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.

Henderson VW. Aging, estrogens, and episodic memory in women. Cogn Behav Neurol. 2009 Dec;22(4):205-14. doi: 10.1097/WNN.0b013e3181a74ce7. Review.

Layout table for additonal information

Responsible Party:	Howard Hodis, University of Southern California
ClinicalTrials.gov Identifier:	NCT00114517
Other Study ID Numbers:	AG0025 R01AG024154 ( U.S. NIH Grant/Contract )
First Submitted:	June 15, 2005
First Posted:	June 16, 2005
Results First Submitted:	April 17, 2017
Results First Posted:	June 8, 2017
Last Update Posted:	June 8, 2017

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