Clinical trial NCT02374021: Treatments Against RA and Effect on FDG-PET/CT
Official title: Treatments Against RA and Effect on FDG-PET/CT (The TARGET Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: rheumatoid arthritis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Columbia University
First posted: 2015-02-27
Enrollment: 159
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
timeFrame: 0, 6 months
Secondary outcomes:
measure: Change From Baseline in the MDS of the Aorta
timeFrame: 0, 6 months
measure: Change From Baseline in the Average TBR of the Aorta
timeFrame: 0, 6 months
measure: Change From Baseline in the Average TBR of the Bilateral Carotids
timeFrame: 0, 6 months
measure: Change From Baseline in the Average TBR of the Index Vessel
timeFrame: 0, 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Clinical Trial Center
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Murrieta
country: United States
facility: Brigid Freyne, MD Inc.
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: West Hills
country: United States
facility: Nazanin Firooz MD, Inc.
state: California
city: Clearwater
country: United States
facility: Robert W. Levin, MD, PA
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development
state: Florida
city: Tampa
country: United States
facility: Southwest Florida Clinical Research Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai- Icahn School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Duncansville
country: United States
facility: Altoona Research Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center- Temple
state: Texas
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
Study officials:
affiliation: Brigham and Women's Hospital
name: Daniel Solomon
role: PRINCIPAL_INVESTIGATOR
References: