Serologically Active, Clinically Stable Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): Prednisone; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Prednisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: SLE; Lupus; Anti-double-stranded DNA antibody; Corticosteroid treatment; Hormone therapy; Complement; Hypertension; Estrogen; SELENA