Safety of Estrogens in Lupus: Birth Control Pills

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000420
• Other study ID #: U01 AR42540 NIAMS-028B
• Secondary ID: U01AR042540
• Status: Completed
• Phase: Phase 3
• First received: November 3, 1999
• Last updated: May 1, 2013
• Start date: June 1997
• Est. completion date: August 2003

Study information

• Verified date: May 2013
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: August 2003
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Ortho-Novum 777

Locations

Country	Name	City	State
United States	Univ. of Michigan Med. Ctr., Rheumatology Division	Ann Arbor	Michigan
United States	Johns Hopkins Hospital, Dept. of Rheumatology	Baltimore	Maryland
United States	Albert Einstein College of Medicine, Jacobi Hospital, Dept. of Rheumatology	Bronx	New York
United States	UNC Medical Center, Dept. of Rheumatology	Chapel Hill	North Carolina
United States	University of Chicago Pritzker School of Medicine	Chicago	Illinois
United States	University of Texas Health Sciences Center	Houston	Texas
United States	UCLA Medical Center, Dept. of Rheumatology	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hospital for Joint Diseases	New York	New York
United States	Hospital for Special Surgery, Dept. of Rheumatology	New York	New York
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Univ. of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Univ. of Pittsburgh, Dept. of Rheumatology	Pittsburgh	Pennsylvania
United States	Medical College of Virginia	Richmond	Virginia
United States	Louisiana School of Medicine, Dept. of Medicine/Immunology	Shreveport	Louisiana

Sponsors (3)

Lead Sponsor	Collaborator
New York University School of Medicine	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Office of Research on Women's Health (ORWH)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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

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

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

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

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

Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, Lockshin M, Merrill JT, Belmont HM, Askanase AD, McCune WJ, Hearth-Holmes M, Dooley MA, Von Feldt J, Friedman A, Tan M, Davis J, Cronin M, Diamond B, Mackay M, Sigler L, Fillius M, Rupel A — View Citation