Skip to main content
OpenTrials
Completed

NCT Number: NCT02374021

Treatments Against RA and Effect on FDG-PET/CT

In a randomized controlled clinical trial, investigators will compare the effects on [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) from two treatment regimens in rheumatoid arthritis (RA) patients deemed methotrexate inadequate responders (MTX-IRs). Two common RA treatments will be compared: triple therapy (sulfasalazine, methotrexate, and hydroxychloroquine) versus tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Arthritis, Rheumatoid Arthritis Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

45 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

About this study

Consenting subjects will be screened for eligibility and randomized to a treatment arm. Subjects will be randomized to a treatment arm with either synthetic disease-modifying antirheumatic drugs (DMARDs) [triple therapy: sulfasalazine, methotrexate, and hydroxychloroquine] or biologic DMARDs [etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening].

Once randomized, a baseline visit will be conducted with each subject. Baseline data collection includes questionnaires, disease activity score, and the first FDG-PET/CT imaging. After the baseline at week 0, subjects will visit with their rheumatologist at weeks 6, 12, 18, and 24 for safety labs and further collection of disease activity scores and questionnaires. The second FDG-PET/CT will be performed at week 24. Blood specimens will be collected at weeks 0, 6, 18, and 24 for bioassays. Subject participation will end after the week 24 visit.

Patients and care providers will be unblinded. The FDG-PET/CT image readers will be blinded to treatment arm as well as timepoint of image acquisition.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Fulfill American College of Rheumatology/European League Against Rheumatism 2010 criteria for RA
  • Men ≥ 45 years and women ≥ 50 years
  • MTX monotherapy for ≥ 8 weeks at ≥ 15mg weekly or ≥ 7.5 mg weekly with a documented intolerance to higher doses
  • No non-biologic DMARDs in preceding two months (other than MTX and HCQ)
  • Disease Activity Score-28 > 3.2
  • Able to sign informed consent

Exclusion criteria

  • Use of biologic DMARD within the past 6 months or use of rituximab ever
  • Current use of >10mg per day of prednisone
  • Use of a high-intensity statin lipid lowering drug or PCSK9 inhibitor in the past 12 months
  • Prior patient reported, physician diagnosed clinical cardiovascular (CV) event
  • Insulin-dependent or uncontrolled diabetes mellitus (DM)
  • Systemic lupus erythematosus (SLE) or other autoimmune and chronic inflammatory diseases (i.e. inflammatory bowel disease, sarcoidosis)
  • Cancer treated in the last 5 years (except basal and squamous cell) or any lymphoma or melanoma
  • Known pregnancy, HIV, Hepatitis B Virus, Hepatitis C Virus, active (or untreated latent) tuberculosis
  • Baseline: liver, renal or blood count abnormalities, Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Known sulfa allergy, macular disease or hypersensitivity to treatments; known demyelinating disease; uncompensated Congestive Heart Failure (CHF)
  • Intra-articular injection within the 4 weeks prior to baseline FDG PET/CT
  • 2 or more high dose radiation scans in the past year (CT scan with contrast, angiogram, SPECT nuclear medicine scan, myocardial/cardiac perfusion scan)

Treatment and study plan

methotrexate

Drug

Subjects entering trial will continue on MTX dose of at least 15mg MTX/week. At the discretion of the treating rheumatologist, may be switched to SQ route.

Other names: Rheumatrex

Sulfasalazine

Drug

1 gm bid

Other names: Azulfidine

Hydroxychloroquine

Drug

200 mg twice daily, not to exceed 6.5mg/kg

Other names: Plaquenil

etanercept

Drug

50 mg SC weekly

Other names: enbrel

Adalimumab

Drug

40 mg SQ every other week

Other names: Humira

Primary outcomes

  1. Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months

    Time frame: 0, 6 months

    The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation.

    FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value [SUVmax and SUVmean, respectively]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.

Secondary outcomes

  1. Change From Baseline in the MDS of the Aorta

    Time frame: 0, 6 months

    The outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.

    FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value [SUVmax and SUVmean, respectively]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.

  2. Change From Baseline in the Average TBR of the Aorta

    Time frame: 0, 6 months

    The outcome was the change in the target to background ratio (TBR) of the aorta as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.

    FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value [SUVmax and SUVmean, respectively]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.

  3. Change From Baseline in the Average TBR of the Bilateral Carotids

    Time frame: 0, 6 months

    The outcome was the change in the target to background ratio (TBR) of the average of the left and right carotids as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The baseline values of the left and right carotids were averaged and then the follow-up values of the left and right carotids were averaged resulting in one value at each time point. Higher values indicate greater vascular inflammation.

    FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value [SUVmax and SUVmean, respectively]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.

  4. Change From Baseline in the Average TBR of the Index Vessel

    Time frame: 0, 6 months

    The outcome was the change in the target to background ratio (TBR) in the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). Higher values indicate greater vascular inflammation.

    FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value [SUVmax and SUVmean, respectively]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • Columbia University

Registry information

Official study title

Treatments Against RA and Effect on FDG-PET/CT (The TARGET Trial)

Acronym: TARGET

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Feb 27, 2015
Registry last updated
Oct 26, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.