Serologically Active, Clinically Stable Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The first part of this study will use the database of a large, ongoing NIH-sponsored lupus study, Safety of Estrogen in Lupus Erythematosus National Assessment. We will examine the levels of a blood protein known as C3a in a series of patient blood samples to see if C3a levels predict lupus flares or are better than other blood tests, and therefore should be used more widely in managing lupus. In the second part of the study we will add or increase prednisone treatment on the basis of abnormalities in blood tests for C3a and dsDNA antibodies. Early treatment based on increases in C3a and dsDNA antibodies, before the patient develops physical signs of disease, may reduce lupus flares and, ultimately, the patient's total steroid exposure. We will follow study participants for 1 year on a monthly basis and do full physical examinations and laboratory evaluations. If C3a and dsDNA antibody levels are increased significantly above baseline levels while a patient is clinically stable, we will give the patient either prednisone or an inactive pill (placebo) for 1 month. We will follow these patients monthly to compare how often lupus flares occur in the two groups. This approach could provide a novel method of preventing lupus flares, using C3a as a sensitive predictor of flare.

Detailed Description
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In lupus, serial evaluation of dsDNA antibody titers and complement (C3 and C4) in blood samples have been useful in assessing disease activity in patients. High levels of C3a, a split product of C3, are particularly sensitive and reflective of lupus flares. Our study looks at whether elevations in C3a can predict lupus flares and how C3a compares with other conventional blood indicators such as dsDNA antibody, C3, C4, and CH50. The utility of serial anti-dsDNA antibodies and complement measurements in clinical decision-making for people with systemic lupus erythematosus (SLE) remains controversial. This study has two specific parts designed to address these issues. In the first, we will take advantage of a unique opportunity to collaborate with a large, multicenter NIH-sponsored protocol, the Safety of Estrogens in Systemic Lupus National Assessment (SELENA) trial. We will perform an observational study of approximately 1,000 women enrolled in the SELENA trial to assess the sensitivity, specificity, and predictive value of anti-dsDNA antibodies, C3, C4, CH50, and C3a desArg. Using samples from patients enrolled in the SELENA study, we will perform subgroup analyses in diverse ethnic groups, patients treated with exogenous estrogen, and patients with chronically depressed CH50. In the second-an interventional study-we will evaluate the effectiveness of short-term corticosteroid treatment in averting flares when elevations of plasma C3a are accompanied by rising anti-dsDNA antibody. We will determine whether corticosteroid treatment reduces the frequency of clinical flare, serological abnormalities, or disease activity in inactive or stable patients. We will explore whether steroids disproportionately exacerbate or initiate comorbid medical conditions (e.g., hypertension, diabetes) that may be more prevalent among minority patients. The studies should result in observations that lead to rational, cost-effective, and evidence-based guidelines that improve the treatment of patients with SLE and-by decreasing the morbidity of disease-result in significant improvement of their quality of life.

Official Title
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Serologically Active, Clinically Stable Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets ACR criteria for SLE Inactive or stable in lupus activity History of positive dsDNA Current prednisone dose no more than 15 mg daily Exclusion Criteria: Active infections Poorly controlled diabetes mellitus Pregnancy Uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisone arm<br>Patients who remained clinically stable but showed serologic evidence of a lupus flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week and 10 mg/day for 1 week. | Drug: Prednisone<br> <br> |
| Placebo Comparator: Placebo<br>Patients who remained clinically stable but showed serologic evidence of a lupus flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week and 10 mg/day for 1 week. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical flare with or without serological flare, or serological flare while clinically stable |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Lupus, Anti-double-stranded DNA antibody, Corticosteroid treatment, Hormone therapy, Complement, Hypertension, Estrogen, SELENA