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

Primary Purpose

Arthritis, Rheumatoid

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Methotrexate
Sulfasalazine
Hydroxychloroquine
Etanercept
Adalimumab
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring rheumatoid arthritis

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Alabama at Birmingham
  • Loma Linda University Clinical Trial Center
  • David Geffen School of Medicine at UCLA
  • Brigid Freyne, MD Inc.
  • Desert Medical Advances
  • University of California San Francisco
  • Nazanin Firooz MD, Inc.
  • Robert W. Levin, MD, PA
  • IRIS Research and Development
  • Southwest Florida Clinical Research Center
  • University of Kentucky
  • The Center for Rheumatology and Bone Research
  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • University of Michigan
  • Washington University Medical Center
  • Dartmouth-Hitchcock Medical Center
  • Northwell Health
  • New York University School of Medicine
  • Mount Sinai- Icahn School of Medicine
  • Columbia University Medical Center
  • University of North Carolina at Chapel Hill
  • Cleveland Clinic
  • Oregon Health & Science University
  • Altoona Research Center
  • University of Pennsylvania
  • University of Pittsburgh Medical Center
  • Metroplex Clinical Research Center
  • University of Texas Health Science Center at Houston
  • Baylor Scott & White Medical Center- Temple
  • Seattle Rheumatology Associates

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Triple therapy (MTX+SSZ+HCQ)

TNF inhibitor (etanercept or adalimumab)

Arm Description

Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).

etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 11, 2015
Last Updated
October 25, 2022
Sponsor
Brigham and Women's Hospital
Collaborators
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT02374021
Brief Title
Treatments Against RA and Effect on FDG-PET/CT
Acronym
TARGET
Official Title
Treatments Against RA and Effect on FDG-PET/CT (The TARGET Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
July 2016 (undefined)
Primary Completion Date
May 2021 (Actual)
Study Completion Date
May 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Columbia University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
rheumatoid arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Triple therapy (MTX+SSZ+HCQ)
Arm Type
Active Comparator
Arm Description
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).
Arm Title
TNF inhibitor (etanercept or adalimumab)
Arm Type
Active Comparator
Arm Description
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Rheumatrex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Sulfasalazine
Other Intervention Name(s)
Azulfidine
Intervention Description
1 gm bid
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
200 mg twice daily, not to exceed 6.5mg/kg
Intervention Type
Drug
Intervention Name(s)
Etanercept
Other Intervention Name(s)
enbrel
Intervention Description
50 mg SC weekly
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira
Intervention Description
40 mg SQ every other week
Primary Outcome Measure Information:
Title
Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
Description
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.
Time Frame
0, 6 months
Secondary Outcome Measure Information:
Title
Change From Baseline in the MDS of the Aorta
Description
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.
Time Frame
0, 6 months
Title
Change From Baseline in the Average TBR of the Aorta
Description
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.
Time Frame
0, 6 months
Title
Change From Baseline in the Average TBR of the Bilateral Carotids
Description
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.
Time Frame
0, 6 months
Title
Change From Baseline in the Average TBR of the Index Vessel
Description
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.
Time Frame
0, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Solomon
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Loma Linda University Clinical Trial Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Brigid Freyne, MD Inc.
City
Murrieta
State/Province
California
ZIP/Postal Code
92563
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Nazanin Firooz MD, Inc.
City
West Hills
State/Province
California
ZIP/Postal Code
91307
Country
United States
Facility Name
Robert W. Levin, MD, PA
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
IRIS Research and Development
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Southwest Florida Clinical Research Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40508
Country
United States
Facility Name
The Center for Rheumatology and Bone Research
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Northwell Health
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Mount Sinai- Icahn School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97329
Country
United States
Facility Name
Altoona Research Center
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
Metroplex Clinical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Baylor Scott & White Medical Center- Temple
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Seattle Rheumatology Associates
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

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Treatments Against RA and Effect on FDG-PET/CT

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