Clinical trial NCT00000420: Safety of Estrogens in Lupus: Birth Control Pills
Official title: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA): Oral Contraceptives
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
SELENA
Oral contraceptives
The pill
Birth control
Condom
Diaphragm
Estrogen
Lupus
Placebo
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Office of Research on Women's Health (ORWH)
First posted: 1999-11-04
Enrollment: 350
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center, Dept. of Rheumatology
state: California
city: Chicago
country: United States
facility: University of Chicago Pritzker School of Medicine
state: Illinois
city: Shreveport
country: United States
facility: Louisiana School of Medicine, Dept. of Medicine/Immunology
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital, Dept. of Rheumatology
state: Maryland
city: Ann Arbor
country: United States
facility: Univ. of Michigan Med. Ctr., Rheumatology Division
state: Michigan
city: Bronx
country: United States
facility: Albert Einstein College of Medicine, Jacobi Hospital, Dept. of Rheumatology
state: New York
city: New York
country: United States
facility: Hospital for Joint Diseases
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery, Dept. of Rheumatology
state: New York
city: Chapel Hill
country: United States
facility: UNC Medical Center, Dept. of Rheumatology
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Philadelphia
country: United States
facility: Univ. of Pennsylvania Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ. of Pittsburgh, Dept. of Rheumatology
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: Richmond
country: United States
facility: Medical College of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Hospital for Joint Diseases
name: Jill P. Buyon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University Hospital, Dept. of Rheumatology
name: Michelle Petri, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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. doi: 10.1191/096120399680411308.
citation: 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.
citation: Buyon JP. Oral contraceptives in women with systemic lupus erythematosus. Ann Med Interne (Paris). 1996;147(4):259-64.
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.
citation: Buyon JP. Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. J Am Med Womens Assoc (1972). 1998 Winter;53(1):13-7.
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, 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.