Clinical Trial: Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: A Multicenter, Open-Label, Proof-of-Activity Study of the Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis

Brief Summary: The purpose of this study is to test the hypothesis that anti-IL-6 therapy is effective for reducing plaque inflammation as measured by fluorine-2-deoxy-D-glucose positron emission tomography (FDG-PET) in patients with rheumatoid arthritis (RA) who are synthetic disease-modifying antirheumatic drugs (dMARD) inadequate responders and are naive to biologic therapy.

Detailed Summary:

This multi-center study will recruit 21 subjects to undergo an open-label tocilizumab treatment for 13-18 weeks in order to examine the efficacy of tocilizumab on plaque inflammation in RA patients. This multi-center study will employ PET/MR imaging of the carotid and coronary arteries and aorta to assess the effect of anti-IL-6 therapy on arterial inflammation in patients with RA who are synthetic dMARD inadequate responders and are naive to biologic therapy.

Secondary, exploratory evaluation will also examine correlations between atherosclerotic plaque inflammation and the inflammatory activity of the rheumatoid joint measured by PET-MR imaging, as well as how the changes in inflammation correlate with lipid and inflammatory biomarkers, and how stress levels are associated with inflammatory activity.

Adults between 50 and 75 years old diagnosed with RA will come in for an initial screening visit to assess for clinical eligibility criteria (visit 1). During the screening period, patient acceptability for the study will be assessed on the basis of medical history, concomitant medications, physical examination, and clinical laboratory test results. The study doctor will review the screening test results and procedures to determine the subject eligibility prior to imaging. Women able to become pregnant will be excluded due to teratogenic side effects.

A FDG-PET/MR imaging study will be performed at a second screening visit (visit 2) to assess for the presence of arterial, plaque and joint inflammation. A serum pregnancy test will be drawn and confirmed to be negative prior to imaging for female subjects of childbearing potential. Acceptability for study participants will be confirmed on the basis of a tissue-to-background ratio (TBR) of greater than or equal to 1.7 in qualify
Sponsor: Massachusetts General Hospital

Current Primary Outcome: Change in arterial FDG uptake (on FDG PET) from baseline to post-treatment [ Time Frame: 13-18 weeks ]

carotid or aortic FDG uptake is measured on PET-MR imaging before and after 12 weeks of tocilizumab treatment.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in arterial FDG uptake within atherosclerotic plaque in carotid/aortic arteries, from baseline to post-treatment [ Time Frame: 13-18 weeks ]
    Changes of inflammation occur within atherosclerotic plaque will be measured on MRI based on change in carotid or aortic plaque FDG uptake before and after 12 weeks treatment
  • change in FDG uptake within joints [ Time Frame: 13-18 weeks ]
    FDG uptake within joints will be measured as an index of inflammation. We will measure changes in joint inflammation before and after treatment
  • LDL [ Time Frame: 13-18 weeks ]
    measure of LDL changes before and after treatment
  • fMRI signal in amygdala [ Time Frame: 13-18 weeks ]
    changes in activity (fMRI) in the amygdala before and after randomization


Original Secondary Outcome: Same as current

Information By: Massachusetts General Hospital

Dates:
Date Received: December 21, 2015
Date Started: May 18, 2016
Date Completion: June 30, 2018
Last Updated: April 25, 2017
Last Verified: April 2017