Conditions: Systemic Lupus Erythematosus
Keywords: hydroxychloroquine
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 187
Healthy volunteers: no

Brief summary:
This project is a multicenter, randomized, placebo-controlled, double-blind clinical trial that is designed to test whether treating patients who are at risk for development of lupus with hydroxychloroquine can slow accumulation of disease features. Effects on clinical progression of symptoms, patient-reported outcomes and changes in the immune markers of response will be measured and toxicity of the treatment will be assessed. This trial is a first step in testing a prevention strategy for lupus.

Detailed description:
Systemic lupus erythematosus (SLE) causes major organ damage and shortens lifespan in relatively young persons. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However, evidenced-based approaches to early treatment interventions and the appropriate target population for these interventions are not available. We propose that individuals who have positivity for antinuclear antibodies (ANAs) and who also exhibit some of the other features that are used to classify SLE, are at high risk of progressing to the full systemic form of this disease. These individuals, who have significant levels of ANA with 1 or 2 additional items from the lupus classification criteria, are considered to have incomplete lupus erythematosus (ILE). We propose to treat ILE patients with hydroxychloroquine (HCQ) in the "Study of Anti-Malarials in Incomplete Lupus Erythematosus" or SMILE trial. The primary objective is to determine whether HCQ treatment can prevent acquisition of additional clinical and immunologic features that define SLE.

The major secondary objectives are to determine whether HCQ treatment: (1) lessens lupus disease activity as measured by standard scoring indices; (2) improves patient reported outcomes (3) prevents accumulation of immunologic abnormalities including autoantibodies and cytokines and (4) has an acceptable toxicity profile. The specific aims of this proposal are:

1. To carry out a double-blind, placebo-controlled, multicenter, randomized trial of HCQ vs. placebo in patients with ILE. The study tests the hypothesis that early use of HCQ can modify disease features so that accumulation of abnormalities leading to a classification of SLE can be significantly slowed.
2. To determine effects of HCQ on disease activity and patient-reported outcomes in patients with ILE.
3. To characterize the immunologic profile of HCQ in ILE-treated patients. Autoantibodies, cytokines and chemokines will be measured on multiplex arrays for developing insights into underlying mechanisms.
4. To quantitatively assess the incidence of ophthalmologic toxicity in HCQ-treated ILE patients. All enrolled patients will have standardized ophthalmologic examinations before and after study treatment. Recommendations for use and monitoring in this patient population will be developed.

The SMILE trial will determine whether or not HCQ should be given to ILE patients, will provide insights into the appropriate target population, and will propose candidate biomarkers to guide treatment decisions. While not part of the Precision Medicine Initiative®, SMILE is consistent with its goals. It will be the first step towards testing the feasibility of disease prevention studies in SLE and will accumulate biological samples in a repository that will be available to the lupus research community for further in-depth mechanistic studies.

Arms:
arm 1: Hydroxychloroquine will be administered as a once daily dose of 200 or 400 mg, based on the patient's weight. Treatment will be for 96 weeks. arm 2: Placebo will be administered as one or two capsules as a single daily dose, based on the patient's weight. Treatment will be for 96 weeks.

Interventions: intervention 1: Hydroxychloroquine intervention 2: Placebo Oral Capsule
Intervention descriptions: intervention 1: Hydroxychloroquine is classified as an anti-malarial and it is has immunomodulatory functions that make it useful for treatment of autoimmune disorders including systemic lupus erythematosus and rheumatoid arthritis. intervention 2: An oral capsule placebo is made to match the active intervention medication hydroxychloroquine.

Protocol document:
Prot_SAP_000.pdf: 



















































































































ICF_001.pdf: