Effects of Hormone Replacement Therapy on Inflammation and Stiffening of Artery Walls
|First Received Date ICMJE||April 11, 2000|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||April 2000|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00005108 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effects of Hormone Replacement Therapy on Inflammation and Stiffening of Artery Walls|
|Official Title ICMJE||Effects of Hormone Therapy on Vascular Inflammation and Compliance|
This study will determine the effects of hormone replacement therapy (estrogen alone or estrogen and progesterone) on the walls of arteries in postmenopausal women. Inflammation and stiffness of artery walls are two risk factors for atherosclerosis-deposits of fatty substances (plaques) that can block the vessel, causing a heart attack or stroke. Estrogen raises the levels of certain substances in the blood that cause vessel inflammation and lowers the levels of others. This study will measure the net effects of estrogen on artery wall inflammation and stiffness.
Postmenopausal women in good health may participate in this study. Volunteers will be screened for eligibility with a complete medical history, heart examination, and blood tests. Participants will be randomly assigned to receive either: 1) hormone therapy (estradiol 2 mg daily alone for women who have had a hysterectomy or estradiol plus micronized progesterone 200 mg daily for women with an intact uterus); or 2) placebo (look-alike pills that contain no active drug). Women in both groups will take pills for 3 months, then no pills for 1 month, and then will crossover to the alternate therapy for 3 months (i.e., those in the original placebo group will take hormones, and those in the hormone group will take placebo). At the end of each 3-month treatment period, participants will undergo the following procedures to assess blood vessel inflammation and stiffness:
Information from this study will increase knowledge about the effects of estrogen on vessel wall inflammation. As such, it may be used in the future to help guide decisions about chronic hormone replacement therapy in postmenopausal women.
Vascular inflammation plays an important role in the pathogenesis of atherosclerosis and may contribute to stiffening of arteries that increases the risk of myocardial infarction and stroke. Accordingly, therapies that reduce vascular inflammation may reduce cardiovascular risk. The effect of estrogen therapy on serum markers of inflammation in postmenopausal women is divergent: Estrogen increases the levels of C-reactive protein, interleukin-6, and matrix metalloproteinase-9 ( MMP-9), but decreases levels of the soluble cell adhesion molecules ICAM-1, VCAM-1 and E-selectin. MMP-9 is secreted by macrophages and cytokine-activated smooth muscle cells, with increased expression in the vicinity of atherosclerotic plaques. Although activation of MMP-9 by estrogen could be deleterious in women with coronary artery disease by digesting the fibrous caps of vulnerable plaques and provoking thrombosis (consistent with the Heart and Estrogen/progestin Replacement Study), activation of MMP-9 in healthy postmenopausal women may remove excess matrix proteins that contribute to arterial stiffness (reduced compliance), thus reducing cardiovascular risk (consistent with the Nurses' Health Study). Reduction of levels of cell adhesion molecules might protect against new plaque development in both groups of women. The purposes of this protocol are to determine the net effects of estrogen therapy on 1) vascular inflammation in postmenopausal women, using MRI/MRA imaging of the carotid arteries, and 2) arterial compliance, derived from carotid ultrasonography and blood pressure measurements.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||January 2002|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Ability to comprehend or unwillingness to sign the consent form.
No use of estrogen therapy within 2 months of this study.
No history of breast cancer, uterine cancer, or estrogen-dependent tumor.
No history of deep vein thrombosis or pulmonary embolus.
No cigarette smokers (within 2 years).
No diabetes mellitus (FBS greater than 120 mg/dL).
Triglycerides less than 400 mg/dL.
Blood pressure less than 160/90 without antihypertensive therapy.
No history of coronary artery disease.
No history of carotid artery disease or stroke.
No history of pancreatitis.
No history of claustrophobia.
No history of involuntary motion disorder.
Specific MRI exclusion criteria (i.e., no pacemaker, no cochlear implants, no AICD, no internal infusion pump, no metal implants or clips in field of view).
No systemic inflammatory disorder (e.g., rheumatoid arthritis, periarteritis nodosa, systemic lupus erythromatosus, temporal arteritis).
Must not have a need for chronic aspirin or NSAID therapy.
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00005108|
|Other Study ID Numbers ICMJE||000111, 00-H-0111|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2002|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP