Aspirin Resistance in Systemic Lupus Erythematosus (SLE)

Vascular Damage in Systemic Lupus Erythematosus (SLE)

This study examine whether patients with lupus respond to aspirin , and if not, if that is related to inflammation. We examine the ability of aspirin to inhibit the production of thromboxane in patients with lupus and controls and see if aspirin insensitive thromboxane production is inhibited by meloxicam.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: aspirin and meloxicam

Detailed Description

Premature cardiovascular disease is a major cause of mortality in patients with systemic lupus erythematosus (SLE) with the risk of myocardial infarction increased up to 50-fold. In addition to defining the mechanisms for accelerated atherosclerosis it is important to define the effects of drugs used to reduce cardiovascular risk in high-risk patients. Low dose aspirin, by inhibiting thromboxane A2 biosynthesis, has profound antiplatelet effects, but some patients have impaired thromboxane suppression - a phenomenon termed aspirin resistance. An explanation is that aspirin-independent thromboxane synthesis may occur through enhanced COX-2 activity, as would occur in an inflammatory condition such as lupus. However, little is known about the effects of low-dose aspirin in SLE. Thus, we propose to test the following hypothesis: 1) that aspirin insensitive thromboxane biosynthesis is increased in patients with lupus and is mediated by increased COX-2 activity.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical School

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written Informed consent.
• Age >18 yrs.
• SLE meeting ACR criteria {Tan, Cohen, et al. 1982 1482 /id} for at least 6 months.(SLE group)
• Stable disease activity as evidenced by no change in immunosuppressive therapy in the past 1 month.
• If female of childbearing potential must use an effective method of birth control

Exclusion criteria.

• Renal disease (creatinine >1.5 mg/dL, dialysis, 2+ or more proteinuria)
• Previous or current history of peptic ulcer disease or gastrointestinal bleed.
• Previous or current thromboembolic or ischemic cardiovascular event (stroke, myocardial infarction, angina) - can do aspirin part of study.
• Currently taking an anticoagulant or antiplatelet agent (besides aspirin).
• Thrombocytopenia (platelet count <135,000)
• Pregnancy
• Allergy to aspirin, NSAIDs
• NSAIDs in the previous week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin and Meloxicam; Arm: Aspirin and Meloxicam Each participant will receive 81 mg aspirin per day for 7 days, followed by meloxicam 7.5 mg daily plus aspirin 81 mg daily for 5 days	Drug: aspirin and meloxicam; aspirin 81 mg daily then aspirin 81 mg plus meloxicam 7.5 mg daily; Other Names: generic, not applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
thromboxane	a hormone of the prostacyclin type released from blood platelets. It induces platelet aggregation and arterial constriction.	after aspirin and after aspirin plus meloxicam

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: C M Stein, M.D., Vanderbilt University

Publications and helpful links

General Publications

• Kawai VK, Avalos I, Oeser A, Oates JA, Milne GL, Solus JF, Chung CP, Stein CM. Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus erythematosus: association with metabolic syndrome. Arthritis Care Res (Hoboken). 2014 Feb;66(2):285-92. doi: 10.1002/acr.22169.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: August 5, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 8, 2008

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 3, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Cyclooxygenase 2 Inhibitors; Aspirin; Meloxicam
• Other Study ID Numbers: HL65082; R01HL065082 (U.S. NIH Grant/Contract)