Atherosclerosis in Rheumatoid Arthritis and Lupus: Restoring Cholesterol Balance

NCT01180361 | Completed

• 1 other identifier: 19-00931
• Study Type: observational
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; systemic lupus erythematosus; atherosclerosis; adenosine

Outcome Measures

Primary Outcomes (1)

• Comparison of 27-hydroxylase level in THP-1 monocytes incubated in human plasma (RA patient, SLE, normal control, psoriatic arthritis).

  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.

  3 years

Secondary Outcomes (1)

• Plasma 27-hydroxycholesterol levels.

  3 years

Study Arms (4)

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• Males and females age 18-65

You may not qualify if:

• No methotrexate or statin therapy in prior 3 months.
• Not on biological therapies.

Sponsors & Collaborators

• NYU Langone Health: lead
• Arthritis Foundation: collaborator

Study Sites (1)

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

Related Publications (3)

• Reiss AB. Effects of inflammation on cholesterol metabolism: impact on systemic lupus erythematosus. Curr Rheumatol Rep. 2009 Aug;11(4):255-60. doi: 10.1007/s11926-009-0036-y.

  PMID: 19691928 BACKGROUND

• Reiss AB, Anwar F, Chan ES, Anwar K. Disruption of cholesterol efflux by coxib medications and inflammatory processes: link to increased cardiovascular risk. J Investig Med. 2009 Aug;57(6):695-702. doi: 10.2310/JIM.0b013e31819ec3c7.

  PMID: 19289972 BACKGROUND

• Reiss AB, Wan DW, Anwar K, Merrill JT, Wirkowski PA, Shah N, Cronstein BN, Chan ES, Carsons SE. Enhanced CD36 scavenger receptor expression in THP-1 human monocytes in the presence of lupus plasma: linking autoimmunity and atherosclerosis. Exp Biol Med (Maywood). 2009 Mar;234(3):354-60. doi: 10.3181/0806-BC-194. Epub 2009 Jan 14.

  PMID: 19144874 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Atherosclerosis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Allison B Reiss, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2010
• First Posted: August 12, 2010
• Study Start: September 1, 2008
• Primary Completion: June 20, 2025
• Study Completion: June 20, 2025
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

US (1)