Effect of HCQ on AnxA5 Resistance Assay in Antiphospholipid (aPL) Positive Patients With and Without Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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This 12 week study will observe patients with and without systemic lupus erythematosus who have persistent antiphospholipid antibodies in the blood who are starting a medicine called hydroxychloroquine. It will measure if these patients have a change in a blood test called the annexin A5 resistance assay over that 12 week period.

Detailed Description
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Antiphospholipid Syndrome (APS) is an autoimmune disorder of blood clotting and pregnancy loss. It is associated with proteins called antiphospholipid antibodies (aPL) in the blood. Blood clotting in this disease occurs for several reasons; one reason involves the interaction of aPL with another protein found on the surface of the cells that line blood vessels (endothelial cells). This protein, called annexin A5 (AnxA5), forms a shield over the surface of these cells. The AnxA5 Resistance Assay is a blood test that can detect when there is a problem with the protective AnxA5 shield on endothelial cell surfaces. This 12 week study will observe patients with persistent aPL in the blood who are starting a medicine called hydroxychloroquine (HCQ). The primary goal of the study is to compare results of the AnxA5 resistance assay from patients before they start taking HCQ and after they have taken it for 12 weeks to see if the results of the blood test change. Our secondary goal is to measure a variety of other blood tests before and after patients have started taking HCQ; these tests include D-dimer, Activated Protein C (APC) Resistance, and aPL titers/status (LA test, aCL ELISA, aß2GPI ELISA, and anti-Domain-I ß2GPI ELISA).

Official Title
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Effect of Hydroxychloroquine on the Annexin A5 Resistance Assay in Antiphospholipid Antibody-Positive Patients With and Without Systemic Lupus Erythematosus

Conditions
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Antiphospholipid Syndrome, Thrombophilia Due to Antiphospholipid Antibody, Systemic Lupus Erythematosus

Intervention / Treatment
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* Other: Phlebotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 to 65 new HCQ (200-400 mg/day) treatment (for all but 5 of 10 control subjects - see below) persistently positive aPL Selected Exclusion Criteria: Steroid use greater than or equal to the equivalent of prednisone 0.5 mg/kg/day at the time of enrollment Heparin use at the time of enrollment Any immunosuppressive drug use within 3 months prior to screening HCQ use within the past 6 months prior to screening visit Another antimalarial agent treatment, Pregnant women, minors, mentally disabled, prisoners Acute thrombosis within 2 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| aPL positive - group 1<br>aPL positive with APS, receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|
| aPL positive - group 2<br>aPL positive with APS and SLE, receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|
| aPL positive - group 3<br>aPL positive without APS but with SLE, receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|
| aPL positive - group 4<br>aPL positive without APS or SLE, receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|
| aPL negative - group 1<br>aPL negative with SLE, receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|
| aPL negative - group 2<br>aPL negative with SLE, not receiving HCQ | Other: Phlebotomy<br>* Subjects will have blood drawn at each of the 3 study visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Annexin A5 resistance assay | The primary goal of the study is to compare results of the AnxA5 resistance assay from patients before they start taking HCQ and after they have taken it for 12 weeks to see if the results of the blood test change. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in D-dimer |  | Baseline and 12 weeks | 
| Change in activated protein C (APC) resistance coagulation assay |  | Baseline and 12 weeks | 
| Change in LA functional coagulation assay |  | Baseline and 12 weeks | 
| Change in anticardiolipin (aCL) ELISA |  | Baseline and 12 weeks | 
| Change in anti-B2-glycoprotein-I (aB2GPI) ELISA |  | Baseline and 12 weeks | 
| Change in anti-Domain-I B2GPI ELISA |  | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiphospholipid syndrome, Antiphospholipid antibodies, Systemic lupus erythematosus, Annexin A5 and Annexin A5 resistance assay