Study of Adalimumab to Lower Cardiovascular Risk in RA Patients With Well Controlled Joint Disease
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|ClinicalTrials.gov Identifier: NCT01893996|
Recruitment Status : Unknown
Verified May 2017 by Jonathan Graf, University of California, San Francisco.
Recruitment status was: Active, not recruiting
First Posted : July 9, 2013
Last Update Posted : May 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis Cardiovascular Disease||Drug: Adalimumab Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Adalimumab to Mitigate Cardiovascular Risk in RA Patients With Well-Controlled Joint Disease|
|Study Start Date :||July 2013|
|Estimated Primary Completion Date :||July 2017|
|Estimated Study Completion Date :||December 2017|
Active Study Drug is Adalimumab (Humira) which is FDA approved to treat rheumatoid arthritis since 2003.
Patients will be randomized 1:1 to receive either adalimumab or placebo for the first 26 weeks of the trial, and then after a 26 week washout period, will be crossed over into the other arm (either placebo or adalimumab) for weeks 52-78.
Other Name: Humira
Placebo Comparator: Placebo
Placebo is inert and matches study drug, including the pre-filled syringe, and is supplied by Abbvie, the study drug manufacturer.
- Change in Endothelial Function [ Time Frame: Weeks 0, 13, 26, 52, 65, 78 ]The primary endpoint is the change in endothelial cell function, as detected by brachial artery flow-mediated dilitation.
- Change in vascular inflammation [ Time Frame: Weeks 0 and 26 ]Vascular inflammation at select body sites will be quantified by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).
- Improvement in HDL function [ Time Frame: Weeks 0,26,52,78 ]HDL function will be assessed by the ability of HDL to promote cholesterol efflux, to prevent low-density lipoprotein (LDL) oxidation and to express higher activity of paraoxonase, an antioxidant enzyme.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01893996
|United States, California|
|University of California San Francisco/San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|Principal Investigator:||Jonathan Graf, MD||University of California, San Francisco|
|Principal Investigator:||Peter Ganz, MD||University of California, San Francisco|