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

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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus; Antiphospholipid Syndrome; Thrombophilia Due to Antiphospholipid Antibody
• Intervention / Treatment: Other: Phlebotomy

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• United States
  • New York
    • New York City, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

For aPL positive groups, subjects must have persistently positive (over at least 12 weeks) antiphospholipid antibodies in the blood.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Montefiore Medical Center
• Investigators: Principal Investigator: Doruk Erkan, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: November 14, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 21, 2011

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: March 23, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Antiphospholipid syndrome; Systemic lupus erythematosus; Antiphospholipid antibodies; Annexin A5 and Annexin A5 resistance assay
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Antiphospholipid Syndrome; Thrombophilia
• Other Study ID Numbers: IRB 10130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No