Treatments Against RA and Effect on FDG-PET/CT

Arthritis, Rheumatoid Clinical Trial

— TARGET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02374021
• Other study ID #: 2014P002747
• Status: Completed
• Phase: Phase 4
• Start date: July 2016
• Est. completion date: May 2021

Study information

• Verified date: October 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Methotrexate
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.
• Sulfasalazine
1 gm bid
• Hydroxychloroquine
200 mg twice daily, not to exceed 6.5mg/kg
• Etanercept
50 mg SC weekly
• Adalimumab
40 mg SQ every other week

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Robert W. Levin, MD, PA	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Altoona Research Center	Duncansville	Pennsylvania
United States	Northwell Health	Great Neck	New York
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	Loma Linda University Clinical Trial Center	Loma Linda	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Brigid Freyne, MD Inc.	Murrieta	California
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai- Icahn School of Medicine	New York	New York
United States	New York University School of Medicine	New York	New York
United States	Desert Medical Advances	Palm Desert	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	IRIS Research and Development	Plantation	Florida
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University Medical Center	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	Southwest Florida Clinical Research Center	Tampa	Florida
United States	Baylor Scott & White Medical Center- Temple	Temple	Texas
United States	Nazanin Firooz MD, Inc.	West Hills	California
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 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.	0, 6 months
Secondary	Change From Baseline in the MDS of the Aorta	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.	0, 6 months
Secondary	Change From Baseline in the Average TBR of the Aorta	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.	0, 6 months
Secondary	Change From Baseline in the Average TBR of the Bilateral Carotids	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.	0, 6 months
Secondary	Change From Baseline in the Average TBR of the Index Vessel	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.	0, 6 months

External Links

•   Study Website