Status and phase
Conditions
Treatments
About
Rheumatoid arthritis patients are at increased risk of cardiovascular disease because of systemic inflammation that can persist even in patients with well-controlled joint disease. We hypothesize that adding an anti-tumor necrosis factor medication, adalimumab, to standard non-biologic therapy for rheumatoid arthritis will improve endothelial function (reduce cardiovascular risk) in these patients. The design of the trial is as follows: 18 month prospective, randomized, double-blind crossover trial comparing the addition of adalimumab to the addition of placebo. The primary endpoint is a change in endothelial cell function, as detected by brachial artery FMD, at 6 months of adalimumab treatment compared to 6 months of placebo.
Full description
Excess mortality associated with RA is due largely to CVD that is not explained by traditional risk factors. Although articular manifestations usually dominate the clinical picture, RA is a systemic inflammatory disease, and systemic inflammation is the thought to be the underlying mechanism responsible for the increased CVD risk associated with RA. Because chronic inflammation can persist in treated RA patients with little or no clinically detectable joint inflammation, treatment to targets based largely on clinically measured joint activity may not adequately suppress the systemic inflammation associated with progression of atherosclerosis. The ACR recommends treatment to a therapeutic target of low disease activity as determined by standardized clinical assessments. We hypothesize that treated RA patients who have reached this ACR target of low disease activity nonetheless have persisting systemic inflammation that contributes to atherogenesis. We further hypothesize that acceleration of RA-directed therapy with systemic anti-inflammatory treatments (TNF inhibition) in patients with low disease activity will improve endothelial function, reduce vascular inflammation and improve the functionality of HDL particles, key biological features in the progression of atherosclerosis and its clinical manifestations.
Trial design: Prospective, randomized, double-blind crossover trial comparing the addition of adalimumab to the addition of placebo.
Study population: 60 RA patients on non-biological DMARDs with low disease activity as determined by a standardized clinical assessment (Disease Activity Score 28 joints [DAS28] < 3.2).
Primary endpoint: Primary endpoint is change in endothelial cell function, as detected by brachial artery FMD, at 6 months of adalimumab treatment compared to 6 months of placebo. We postulate that anti-TNF therapy with adalimumab will lead to an absolute increase of 2% in FMD, which typically translates into a 15% reduction in cardiovascular event rates.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Use of an anti-TNF or other biologic medication (Including but not limited to abatacept, rituximab, or tocilizumab) within the previous 12 months.
Prior history of MI, CVA, CABG, PTCA, or peripheral vascular disease
SBP > 140/90 at two months prior to study enrollment
Diabetes mellitus requiring insulin therapy
The following laboratory parameters at the Screening visit
Purified protein derivative (PPD) test of > 5 mm induration regardless of prior BacilleCalmette Guerin vaccine administration or positive QuantiFERON®-TB Gold In-Tube Test (QFT-G_IT) without documentation of completed treatment or evidence of ongoing treatment of latent tuberculosis (TB) for 30 days. Subjects with active TB infection are excluded.
History of positive PPD, positive QuantiFERON®-TB Gold In-Tube Test (QFT-G_IT), or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure
Prednisone dose > 10 mg/day (or equivalent dose of another corticosteroid) within 1 month of randomization
Presence of open leg ulcers
Chronic or persistent infection including but not limited to human immunodeficiency virus [HIV],hepatitis B, hepatitis C, listeriosis, TB, or other opportunistic infection)
Active infection or severe infections requiring hospitalization or treatment with intravenous(IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to randomization, or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to randomization
Receipt of a live vaccine within 4 weeks prior to randomization
History of malignancy within the past 5 years other than treated localized carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma
Any medical condition, such as uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, known coronary artery disease or known significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association classes III or IV), recent cerebrovascular accidents, severe, progressive or uncontrolled neurological disease, and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol
Women of childbearing potential who are sexually active and who do not agree to practiceone of the following methods of contraception during the duration of the study
Pregnant (all women of childbearing potential must have a negative serum pregnancy test) or breastfeeding
Any investigational agent within the earlier of 4 weeks or 5 half-lives prior to randomization
History of drug or alcohol abuse within 6 months prior to randomization
Known allergy or hypersensitivity to any study products
Any psychiatric disorder that prevents the subject from providing informed consent
Inability or unwillingness to follow the protocol
Any condition or treatment, which in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial
Any individual who plans to start or stop or change the dose of lipid lowering medication,antihypertensive medication, NSAIDS, Cox-2 inhibitors, aspirin within 1 month of the study or during the study.
Primary purpose
Allocation
Interventional model
Masking
63 participants in 2 patient groups, including a placebo group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal