Safety of Estrogens in Lupus: Birth Control Pills

NCT ID: NCT00000420

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-06-30
• Study Completion Date: 2003-08-31

Brief 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.

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Ortho-Novum 777

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Office of Research on Women's Health (ORWH)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Principal Investigators

Jill P. Buyon, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital for Joint Diseases

Michelle Petri, MD

Role: STUDY_DIRECTOR

Johns Hopkins University Hospital, Dept. of Rheumatology

Locations

UCLA Medical Center, Dept. of Rheumatology

Los Angeles, California, United States

University of Chicago Pritzker School of Medicine

Chicago, Illinois, United States

Louisiana School of Medicine, Dept. of Medicine/Immunology

Shreveport, Louisiana, United States

Johns Hopkins Hospital, Dept. of Rheumatology

Baltimore, Maryland, United States

Univ. of Michigan Med. Ctr., Rheumatology Division

Ann Arbor, Michigan, 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

Albert Einstein College of Medicine, Jacobi Hospital, Dept. of Rheumatology

The Bronx, New York, United States

UNC Medical Center, Dept. of Rheumatology

Chapel Hill, North Carolina, 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

University of Texas Health Sciences Center

Houston, Texas, United States

Medical College of Virginia

Richmond, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Buyon JP. Clinical trials in systemic lupus erythematosus. Curr Rheumatol Rep. 2000 Feb;2(1):11-12. doi: 10.1007/s11926-996-0062-y. No abstract available.

Reference Type: BACKGROUND

PMID: 11123033 (View on PubMed)

Petri M, Buyon J, Kim M. Classification and definition of major flares in SLE clinical trials. Lupus. 1999;8(8):685-91. doi: 10.1191/096120399680411281.

Reference Type: BACKGROUND

PMID: 10568907 (View on PubMed)

Kim MY, Buyon JP, Petri M, Skovron ML, Shore RE. Equivalence trials in SLE research: issues to consider. Lupus. 1999;8(8):620-6. doi: 10.1191/096120399680411308.

Reference Type: BACKGROUND

PMID: 10568898 (View on PubMed)

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. doi: 10.1002/art.1780400831. No abstract available.

Reference Type: BACKGROUND

PMID: 9259444 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 8952745 (View on PubMed)

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.

Reference Type: BACKGROUND

Buyon JP. Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. J Am Med Womens Assoc (1972). 1998 Winter;53(1):13-7.

Reference Type: BACKGROUND

PMID: 9458619 (View on PubMed)

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, Licciardi F, Buyon JP; OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med. 2005 Dec 15;353(24):2550-8. doi: 10.1056/NEJMoa051135.

Reference Type: RESULT

PMID: 16354891 (View on PubMed)

Other Identifiers

U01AR042540

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01 AR42540 NIAMS-028B

Identifier Type: -

Identifier Source: org_study_id