Safety of Estrogens in Lupus: Hormone Replacement Therapy

NCT ID: NCT00000419

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-04-30
• Study Completion Date: 2002-08-31

Brief Summary

Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test whether postmenopausal women with systemic lupus erythematosus (SLE, or lupus) can safely use the hormone estrogen. In this part of the study, we will look at the effects of estrogen replacement therapy on the activity and severity of disease in women with SLE.

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 hormone replacement therapy (HRT) to women with SLE because of the widely held view that such treatment 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 HRT.

We will examine, in a multicenter, randomized, double-blind, placebo-controlled trial, the effect of hormonal replacement with conjugated estrogens on disease activity in postmenopausal women with SLE. We will recruit patients from clinics and private practices that include over 4,000 women with SLE, most belonging to minority groups.

We will give patients hormones for 1 year.

NOTE: This trial has been terminated as of August 2002 upon recommendation of the Data Safety Monitoring Board (DSMB), based on the findings of the WHI Trial. Study subjects have discontinued study drug but will continue followup visits to study doctors through May 2003

Conditions

Systemic Lupus Erythematosus

Study Design

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

Interventions

Premarin and Provera

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female
• Unequivocal diagnosis of SLE
• Inactive disease or stable on 0.5 mg/kg/day or less of prednisone
• Chemical evidence of menopause or have stopped periods for at least 6 months

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 (HRT or OCP) for >1 month at any time after SLE diagnosis
• FSH <40
• Premenopausal myocardial infarction

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 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 Buyon, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital for Joint Diseases, Department of Rheumatology

Michelle Petri, M.D.

Role: STUDY_DIRECTOR

Johns Hopkins Hospital, Department of Rheumatology

Locations

UAB Medical Center

Birmingham, Alabama, United States

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

Shreveport, Louisiana, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Univ. of Michigan Med. Ctr., Rheumatology Div.

Ann Arbor, Michigan, United States

Hospital for Joint Diseases

New York, New York, United States

Hospital for Special Surgery

New York, New York, United States

Albert Einstein College of Medicine, Jacoby 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, Ambulatory Care Center

Richmond, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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. 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)

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)

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, 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, Petri MA, Kim MY, Kalunian KC, Grossman J, Hahn BH, Merrill JT, Sammaritano L, Lockshin M, Alarcon GS, Manzi S, Belmont HM, Askanase AD, Sigler L, Dooley MA, Von Feldt J, McCune WJ, Friedman A, Wachs J, Cronin M, Hearth-Holmes M, Tan M, Licciardi F. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):953-62. doi: 10.7326/0003-4819-142-12_part_1-200506210-00004.

Reference Type: RESULT

PMID: 15968009 (View on PubMed)

Other Identifiers

U01AR042540

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01 AR42540 NIAMS-028A

Identifier Type: -

Identifier Source: org_study_id