Atherosclerosis in Rheumatoid Arthritis and Lupus: Restoring Cholesterol Balance

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Winthrop University Hospital
Sponsor:
Collaborator:
Arthritis Foundation
Information provided by (Responsible Party):
Allison B. Reiss, MD, Winthrop University Hospital
ClinicalTrials.gov Identifier:
NCT01180361
First received: August 10, 2010
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

Hypothesis: SLE and RA increase risk of myocardial infarction (MI, heart attack). Immune reactants in the circulation of SLE patients downregulate cholesterol efflux proteins 27-hydroxylase and ABCA1 and upregulate scavenger receptor CD36, thus encouraging cholesterol accumulation. Adenosine A2A receptor agonist or statin treatment of cells exposed to SLE plasma (or immune complexes or cytokine-enriched plasma fractions from SLE patients) may ameliorate inflammatory properties of their plasma, lessening its atherogenic potency.

Rationale: SLE and RA plasma contain components not present in significant levels in normal plasma that could, individually or acting together, affect 27-hydroxylase, ABCA1 and CD36 expression. Candidate components include autoantibodies, immune complexes, and various cytokines. Statins reduce major cardiovascular events and death. Modulation of adenosine signaling participates in regulation of 27-hydroxylase and ABCA1. As a potential preventative and therapeutic approach to atherosclerotic cardiovascular disease, the investigators evaluate the effect of A2A receptor agonists and statins on atherogenic parameters in SLE and RA plasma.

Experimental Plan: Quantitate 27-hydroxylase and several other proteins involved in cellular cholesterol uptake and excretion in THP-1 monocytes/macrophages and HAEC after exposure to plasma and plasma components from SLE patients (and controls) ± lipid loading with acetylated LDL with/without addition of A2AR agonist, statin, or both. Determine relative impact of immune complexes and cytokines on expression of proteins involved in cholesterol flux. Determine levels of proteins involved in cellular cholesterol influx/efflux in peripheral blood mononuclear cells isolated from RA, SLE and psoriatic arthritis patients and normal controls at baseline, then following incubation in culture media alone or with statin, adenosine A2A agonist or both statin + A2AR agonist.


Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Atherosclerosis in RA and Lupus: Restoring Cholesterol Balance

Resource links provided by NLM:


Further study details as provided by Winthrop University Hospital:

Primary Outcome Measures:
  • Comparison of 27-hydroxylase level in THP-1 monocytes incubated in human plasma (RA patient, SLE, normal control, psoriatic arthritis). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The activated proinflammatory state of monocytes in RA and SLE subjects constitutes a novel parameter of risk associated with this disorder, related to altered expression of cholesterol transport genes. 27-hydroxylase level may be diminished by the plasma of patents with autoimmune rheumatic disorders.


Secondary Outcome Measures:
  • Plasma 27-hydroxycholesterol levels. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Plasma 27-hydroxycholesterol may be lower in RA and SLE patients than in healthy controls due to less 27-hydroxylase expression and activity in RA and lupus.


Biospecimen Retention:   Samples Without DNA

plasma


Estimated Enrollment: 160
Study Start Date: September 2008
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Active SLE patients
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Fulfill 1982 ACR revised criteria for SLE. SLE activity status designated using the SLEDAI disease activity index. Patients excluded if previous documentation of a connective tissue disorder other than SLE.
Psoriatic arthritis
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Diagnosed according to criteria described by McGonagle et al (McGonagle, D., Conaghan, P.G., and Emery, P. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum 1999; 42: 1080-1086.)
Normal controls
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Healthy volunteers. Not on corticosteroids.
Active RA patients
Age 18-65, male and female, no methotrexate or statin therapy in prior 3 months. Not on biological therapies. satisfy at least 4 of the 7 revised criteria (1987) for the classification of RA

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Lupus patients, rheumatoid arthritis patients, psoriatic arthritis patients, healthy volunteers in Nassau County NY

Criteria

Inclusion Criteria:

  • Males and females age 18-65

Exclusion Criteria:

  • No methotrexate or statin therapy in prior 3 months.
  • Not on biological therapies.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01180361

Contacts
Contact: Allison B Reiss, MD 516-663-3455 areiss@winthrop.org

Locations
United States, New York
Winthrop University Hospital Recruiting
Mineola, New York, United States, 11501
Contact: Steven Carsons, MD    516-663-4751    SCarsons@winthrop.org   
Principal Investigator: Allison B Reiss, MD         
Sub-Investigator: Steven Carsons, MD         
Sponsors and Collaborators
Winthrop University Hospital
Arthritis Foundation
Investigators
Principal Investigator: Allison B Reiss, MD Winthrop University Hospital
  More Information

Publications:
Responsible Party: Allison B. Reiss, MD, Associate Professor Of Medicine, Winthrop University Hospital
ClinicalTrials.gov Identifier: NCT01180361     History of Changes
Other Study ID Numbers: 08310
Study First Received: August 10, 2010
Last Updated: January 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Winthrop University Hospital:
rheumatoid arthritis
systemic lupus erythematosus
atherosclerosis
adenosine

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Atherosclerosis
Arteriosclerosis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 21, 2014