OBJECTIVES: I. Determine the effect of oral contraceptives containing low-dose synthetic estrogens and progestins on disease activity in premenopausal women with inactive, stable, or moderate systemic lupus erythematosus (SLE). II. Determine the effect of hormone replacement therapy with conjugated estrogens and progestins on disease activity in postmenopausal women with inactive, stable, or moderate SLE.
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Primary Purpose: Treatment
- Masking: Double
PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age/menopausal status (35 and under/premenopausal vs 50 and over/postmenopausal). Both strata are randomized to one of two treatment arms. Stratum 1 (Premenopausal/Oral contraceptives): Patients receive either oral ethinyl estradiol and norethindrone or placebo daily for 28 days beginning on the Sunday following the first day of the menstrual cycle. Stratum 2 (Postmenopausal/Hormone replacement therapy): Patients receive either oral estradiol and medroxyprogesterone or placebo on days 1-12 monthly. Treatment continues in both arms of both strata for a total of 13 courses in the absence of a severe disease flare-up or other complication that would preclude further study participation. All patients are followed at 1 year.
- Drug: estradiol
- Drug: ethinyl estradiol
- Drug: medroxyprogesterone
- Drug: norethindrone
Participating in This Clinical Trial
PROTOCOL ENTRY CRITERIA: –Disease Characteristics– Established systemic lupus erythematosus meeting American College of Rheumatology criteria Inactive disease Systemic Lupus Erythematosus Activity Index (SLEDAI) score no greater than 4 No increase in score of more than 2 from baseline over the past 3 months Receiving the equivalent of 5 mg or less of prednisone per day OR Stable/active disease SLEDAI score 5-12 No increase in score of more than 2 from baseline over the past 3 months Prednisone dose up to 0.5 mg/kg/day for control of underlying disease allowed if stable dose for at least 3 weeks No concurrent severe disease activity as defined by any of the following:
- Acute renal disease (i.e., rising creatinine levels, cellular sediment, or increasing proteinuria) – Involvement of 3 or more organ systems requiring more than the equivalent of 0.5 mg/kg/day of prednisone – Necessity of immediate hospitalization for symptom control No presence of a high titer IgG, IgM, or IgA antiphospholipid antibodies (aPL) GPL and MPL no more than 40 APL no more than 50 No features of primary antiphospholipid antibody syndrome –Prior/Concurrent Therapy– Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: See Disease Characteristics Radiotherapy: Not specified Surgery: Prior hysterectomy allowed –Patient Characteristics– Age: 35 and under for oral contraceptive stratum (premenopausal) 50 and over for hormone replacement therapy stratum (postmenopausal) Menopausal status: – Premenopausal for oral contraceptive stratum – Postmenopausal for hormone replacement therapy stratum – Follicle-stimulating hormone greater than 40 mIU/mL OR Amenorrhea for 6 months Performance status: See Disease Characteristics Hematopoietic: Not specified Hepatic: – No hepatic dysfunction – No tumors of the liver Renal: See Disease Characteristics Cardiovascular: – No uncontrolled high blood pressure requiring frequent change in medication – Concurrent hypertension controlled with stable medication allowed – No history of spontaneous superficial or deep venous thrombosis or arterial thrombosis – No prior myocardial infarction – Oral contraceptive stratum: No angina No diastolic blood pressure greater than 90 mm Hg or systolic blood pressure greater than 140 mm Hg on 3 separate determinations – Hormone replacement therapy stratum: No diastolic blood pressure greater than 95 mm Hg or systolic blood pressure greater than 145 mm Hg on 3 separate determinations Pulmonary: No history of pulmonary embolus Other: – Not pregnant – Oral contraceptive stratum: Negative pregnancy test Fertile patients must use effective barrier contraception – No prior gynecologic malignancy or breast malignancy – No undiagnosed vaginal bleeding – No diabetes (present prior to use of glucocorticoids) requiring oral hypoglycemic medications or insulin – No congenital hyperlipidemia – No complicated migraines (i.e., associated with neurological sequelae)
Gender Eligibility: Female
Minimum Age: N/A
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- National Center for Research Resources (NCRR)
- University of Alabama at Birmingham
- Overall Official(s)
- Graciela S. Alarcon, Study Chair, University of Alabama at Birmingham
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