This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The increased risk of heart attacks and strokes among patients with systemic lupus erythematosus (SLE) was thought to be from 'traditional risk factors' such as high cholesterol and high blood pressure, and from blood vessel diseases that are common in SLE. Treating heart disease in SLE could improve illness and increase life span. The effect of sex hormones on the blood vessel wall in important in lupus. Estrogen breakdown is abnormal in women with lupus, suggesting that an abnormality of sex steroids like estrogen may increase lupus flares. Estrogen is known to provide protection against heart attacks. Dehydroepiandrosterone (DHEA), a weak male hormone, decreases prednisone requirements in lupus patients, possibly by decreasing the effects of the immune system. DHEA has been reported in animals to reduce plaque build-up in blood vessels, making it an attractive 'add-on' therapy in lupus. DHEA administration may strike a favorable balance by providing protection against plaque build up in blood vessels through estrogen and weaken the immune system through androgen. To evaluate effect of DHEA on blood vessel walls, we will measure its effect on several things that tell us about risk for heart disease and stroke: ultrasound pictures of the blood flowing through one of the blood vessels in the arm (the brachial artery), and blood tests that help us know the risk a person has for heart disease. 20 adult women with lupus will be randomly picked from the rheumatology clinics. All will be patients of UMHS rheumatologists or fellows. Patients whom we enroll will still have menstrual periods, will not smoke, will not have diabetes and will be taking no more than 10mg of prednisone. We will fully explain the study and answer all questions about it, then ask patients to read and sign a consent form so that they fully understand the risks and benefits of being in the study. We will keep any information about patients in the study confidential, and people's names will not be on any documents. Instead, patients will be given a code number, which will not reveal who they are to anyone looking at the study data. We think our study will have around 40% Anglo patients, 60% African-American and Asian patients. Patients will randomly be put into one of two groups. One group will get DHEA and one group will get a sugar tablet or 'placebo' for 10 weeks. Then, the two groups will switch treatments after 6 weeks of taking either DHEA or sugar pill. At that time, they will switch to the tablets that they were not taking during the first 10 weeks. We hope to learn if DHEA therapy can not only improves lupus symptoms like joint pain, but can also help prevent events like heart attacks in lupus patients. Of interest in atherosclerosis and lupus is the effect of sex hormones on the vascular endothelium. Estrogen metabolism is abnormal in women with lupus, suggesting that an abnormality of sex steroids may contribute to disease activity. However estrogen is known to upregulate nitric oxide, providing a protective effect on vascular endothelium as an antiatherogenic, antiproliferative and antithrombotic factor. Dehydroepiandrosterone (DHEA), a weak androgen, decreases corticosteroid requirements in lupus patients, possibly through immunosuppressive effects. DHEA has been reported in animal studies to reduce atherosclerosis, making it an attractive adjuvant therapy in lupus. As a proposed modulator of sex hormone levels in lupus patients, DHEA administration may strike a favorable balance by providing protection against atherosclerosis through estrogenic effects and an immunosuppressive role through androgenic effects. To evaluate effect of DHEA on endothelial function, we will measure its effect on several markers of cardiovascular risk: flow-mediated dilatation of the brachial artery (FMD), a noninvasive measure of endothelial function, and serum biomarkers of cardiovascular disease. 20 adult female patients meeting ACR criteria for SLE willbe randomly selected from the rheumatology clinics. All will be patients of UMHS faculty rheumatologists or fellows. Eligible patients will be premenopausal, non-smokers, non-diabetic and on a dose of prednisone no greater than 10mg. Written informed consent will be obtained, and the project explained by a study investigator. Research records will be linkable but coded. Approximately 40% will be Caucasian, 60% African-American and Asian. Patients will be randomized in double-blinded fashion to DHEA or placebo for 10 weeks, then crossed-over to the alternate treatment arm after a six week washout period.
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