Safety of Estrogens in Lupus: Birth Control Pills

Condition(s) targeted: Systemic Lupus Erythematosus

Intervention: Ortho-Novum 777 (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: New York University School of Medicine

Official(s) and/or principal investigator(s):
Jill P. Buyon, MD, Principal Investigator, Affiliation: Hospital for Joint Diseases
Michelle Petri, MD, Study Director, Affiliation: Johns Hopkins University Hospital, Dept. of Rheumatology

Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test

whether women with systemic lupus erythematosus (SLE or lupus) can safely use estrogen. We will determine this by looking at the effects of oral contraceptives (birth control pills, also known as "the pill") on disease activity and severity in women with SLE. The results of the study will show whether it is safe for women with SLE to use the pill.

Official title: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA): Oral Contraceptives

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Detailed description: This study tests the effect of exogenous female hormones on disease activity and severity in women with systemic lupus erythematosus (SLE). Physicians generally do not prescribe oral contraceptives (OCs) to women with lupus because of the widely held view that these drugs can activate SLE. This practice is based on the greater incidence of SLE in women than in men, biologic abnormalities of estrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving exogenous hormones, and a single retrospective study in patients with preexisting renal disease. By contrast, recent retrospective studies suggest that the rate of flare is not significantly increased in patients taking OCs. The preexisting data is insufficient to warrant the dismissal of a potentially important birth control option in a disease that predominantly affects women in their reproductive years and whose fertility is not altered by the disease. Moreover, the use of OCs to preserve fertility in patients taking cyclophosphamide and the use of estrogens to prevent coronary artery disease and postmenopausal and steroid-induced osteoporosis are timely considerations. We will attempt to define, in a multicenter, randomized, double-blind, placebo-controlled trial, the effect of OCs containing low-dose synthetic estrogens and progestins on disease activity in women with SLE. Because the research hypothesis is that OCs do not increase the risk of flares, we have designed the study to be able to detect minimal increases in the rate of flares in patients taking OCs. We will enroll patients with inactive, stable, or moderate disease requiring less than 0. 5 mg prednisone per kg of bodyweight per day over a 2-year period and randomize them to receive birth control pills or placebo pills for 12 months. During that time, the patient must use condoms or a diaphragm as birth control. We will recruit patients from clinics and private practices that include over 4,000 women with SLE, most belonging to minority groups.

Minimum age: 18 Years. Maximum age: 39 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Female

- Unequivocal diagnosis of SLE

- Inactive disease or be stable on 0. 5 mg/kg/day or less of predisone

- Must be between 18 and 39 years old if non-smoker

- Must be between 18 and 35 years old if smoker

Exclusion Criteria:

- Blood pressure >145/95 on three occasions

- Deep vein, arterial thrombosis or pulmonary embolus

- GPL >40; MPL >40; APL >50; dRVVT >37 sec

- APL antibody syndrome ever

- Gynecologic or breast cancer

- Hepatic dysfunction or liver tumors

- Diabetes mellitus (NOT due to steroids) with vascular disease

- Congenital hyperlipidemia

- Complicated migraine

- Severe disease activity (SLEDAI >12)

- Increase in SLEDAI >2 points in 3 months

- Unexplained vaginal bleeding

- Use of estrogen (OCP) for >1 month at any time after SLE diagnosis

- Present pregnancy

- Angina or MI due to APS

- Age >35 yrs. for smokers; >39 yrs. for nonsmokers

UCLA Medical Center, Dept. of Rheumatology, Los Angeles, California 90024, United States

University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, United States

Louisiana School of Medicine, Dept. of Medicine/Immunology, Shreveport, Louisiana 71130-3932, United States

Johns Hopkins Hospital, Dept. of Rheumatology, Baltimore, Maryland 21205, United States

Univ. of Michigan Med. Ctr., Rheumatology Division, Ann Arbor, Michigan 48109-0358, United States

Albert Einstein College of Medicine, Jacobi Hospital, Dept. of Rheumatology, Bronx, New York 10461, United States

Hospital for Joint Diseases, New York, New York 10003, United States

Hospital for Special Surgery, Dept. of Rheumatology, New York, New York 10021, United States

UNC Medical Center, Dept. of Rheumatology, Chapel Hill, North Carolina 27599-7280, United States

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, United States

Univ. of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, United States

Univ. of Pittsburgh, Dept. of Rheumatology, Pittsburgh, Pennsylvania 15213, United States

University of Texas Health Sciences Center, Houston, Texas 77030, United States

Medical College of Virginia, Richmond, Virginia 23219, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Related publications:

Buyon JP. Clinical trials in systemic lupus erythematosus. Curr Rheumatol Rep. 2000 Feb;2(1):11-12. Review.

Petri M, Buyon J, Kim M. Classification and definition of major flares in SLE clinical trials. Lupus. 1999;8(8):685-91.

Kim MY, Buyon JP, Petri M, Skovron ML, Shore RE. Equivalence trials in SLE research: issues to consider. Lupus. 1999;8(8):620-6.

Buyon JP, Dooley MA, Meyer WR, Petri M, Licciardi F. Recommendations for exogenous estrogen to prevent glucocorticoid-induced osteoporosis in premenopausal women with oligo- or amenorrhea: comment on the American College of Rheumatology recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum. 1997 Aug;40(8):1548-9.

Buyon JP. Oral contraceptives in women with systemic lupus erythematosus. Ann Med Interne (Paris). 1996;147(4):259-64. Review.

Buyon JP, Wallace DJ. The endocrine system, use of exogenous estrogens, and the urogenital tract. In Dubois' Lupus Erythematosus, 6th edition. Wallace DJ, Hahn BH, eds. Philadelphia: Lippincott Williams & Wilkins, 2002; pp. 821-841.

Buyon JP. Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. J Am Med Womens Assoc. 1998 Winter;53(1):13-7. Review.

Starting date: June 1997
Last updated: May 1, 2013