Clinical trial NCT00731302: Aspirin Resistance in Systemic Lupus Erythematosus (SLE)
Official title: Vascular Damage in Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-08-08
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: thromboxane
timeFrame: after aspirin and after aspirin plus meloxicam
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt University Medical School
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: C M Stein, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.