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.

Condition	Treatment or Intervention
Systemic Lupus Erythematosus	Drug: estradiol  Drug: ethinyl estradiol  Drug: medroxyprogesterone  Drug: norethindrone

Further Study Details: 

Expected Total Enrollment:  970

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.

Genders Eligible for Study:  Female

Criteria

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)

Alabama
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States
California
      University of California Los Angeles, Los Angeles,  California,  90095-6951,  United States
      University of California-San Francisco, San Francisco,  California,  94143,  United States
Illinois
      Pritzker School of Medicine, Chicago,  Illinois,  60637,  United States
Louisiana
      Louisiana State University School of Medicine, Shreveport,  Louisiana,  71130-3932,  United States
Maryland
      Johns Hopkins University School of Medicine, Baltimore,  Maryland,  21205,  United States
Michigan
      University of Michigan Health Systems, Ann Arbor,  Michigan,  48109,  United States
New York
      Hospital for Joint Diseases, New York,  New York,  10003,  United States
      Hospital for Special Surgery, New York,  New York,  10021,  United States
      Montefiore Medical Center, Bronx,  New York,  10467-2490,  United States
      Rheumatology Associates of Long Island, Port Jefferson Station,  New York,  11776,  United States
      Saint Luke's-Roosevelt Hospital Center, New York,  New York,  10019,  United States
North Carolina
      University of North Carolina, Chapel Hill,  North Carolina,  27599,  United States
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh, Pittsburgh,  Pennsylvania,  15260,  United States
Texas
      University of Texas- Houston Medical School, Houston,  Texas,  77030,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States

Study chairs or principal investigators

Graciela S. Alarcon,  Study Chair,  UAB Comprehensive Cancer Center   

Study ID Numbers:  199/15327; UAB-SELENA
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006133
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08