An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
The purpose of this study is to show that patients with gout suffer from chronic inflammation of their joints, observable by MRI, even in the absence of symptomatic gouty attacks. Secondary end-points of this study will include analyzing the effects of uric acid-lowering therapy (specifically with the FDA approved medication Febuxostat) in a subgroup of patients, checking for the presence of inflammatory markers to see if there is any correlation with the proposed chronic inflammation, and evaluating for other characteristic findings of gout on MRI.
Other: Magnetic Resonance Imaging
Other: Plain Radiographs
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Shifting the Paradigm of Gout: An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.|
- Presence of synovial pannus in index joint. [ Time Frame: MRI and baseline uric acid level will be performed upon enrollment in the study. ] [ Designated as safety issue: No ]The primary aim of this study will be to determine the percentage of patients with known gout who have evidence of chronic ongoing synovial-based inflammatory disease, i.e. synovial pannus, in their "index joint", and determine if there is a correlation of the prevalence and severity of synovial pannus in the "index joint" with the patients' serum urate levels on the day of their MRI.
- Effect of urate-lowering therapy (specifically with febuxostat [Uloric]) on synovial pannus. [ Time Frame: Upon enrollment into study, and at month 9. ] [ Designated as safety issue: No ]A sub-study in a subgroup of patients will analyze the effect of urate-lowering therapy (specifically with febuxostat [Uloric]) on synovial pannus in the "index joint" by comparing the baseline MRI with a repeat MRI of the same joint after 9 months of therapy with febuxostat.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
All study participants: Standard demographics will be obtained including a baseline serum urate, creatinine, and hs-CRP. Study subjects will have their "index joint" determined (the joint that is most often involved with acute attacks of gout in each particular patient). A plain radiograph of the "index joint" will be obtained, as well as an MRI with and without gadolinium enhancement to assess for presence and degree synovial pannus.
Other: Magnetic Resonance Imaging
An MRI (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).
Other Name: 3 Tesla MRIOther: Plain Radiographs
Plain radiographs of "index joint" will be obtained and reviewed by two independent readers (radiologists)
Other Name: Xrays
Febuxostat Sub-Study Arm
To analyze the effect of urate-lowering therapy (specifically with febuxostat [Uloric]) on the synovial pannus in the "index joint" of a subgroup of patients. Subjects not currently on any urate-lowering therapy, or on a serum urate lowering drug other than febuxostat (Uloric) and who have a serum urate level of > or = to 9.0, will be treated with febuxostat (Uloric) and their serum urate level will be followed at months 1, 3, 6, and 9. MRI (with and without gadolinium) of the same "index joint" will be repeated at month 9 to assess for the presence and degree of synovial pannus. Because initiation of urate-lowering therapy can induce acute attacks of gout, these subjects will also be started on colchicine as a prophylactic (and remain on colchicine for 6 months).
All subjects in the sub-study will be started on febuxostat 40mg daily at baseline. If their serum urate level is > 6.0 at months 1 or 3, then the febuxostat dose will be increased to 80mg daily.
Other Name: UloricDrug: Colchicine
Colchicine will be dosed at 0.6mg by mouth BID for the first three months then 0.6mg daily from months 3 to 6, and then discontinued at month 6.
Other Name: Colcrys
The clinical history of untreated gout transitions from an acute intermittent arthritis to a chronic inflammatory arthritis. This tells us that at some point the inflammation associated with gout does not abate. Our group recently completed an advanced imaging study in patients with early gout that suggested nearly 60% of subjects had synovial pannus during intercritical gout. This is likely more prevalent in patients with more advanced gout. The presence of synovial pannus also likely correlates with serum urate levels. The primary aim of this study will be to determine the percentage of patients with known gout who have evidence of chronic ongoing synovial-based inflammatory disease, determine the degree of this inflammation, and correlate it with their serum urate levels. Secondary endpoints will include assessments for the presence of other characteristic findings of gout on these MRI (i.e. erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema, and soft tissue edema). We will also be checking serum high-sensitivity CRP levels to evaluate for any correlation with synovial pannus, and assess baseline radiographs of the "index" joint for the presence of erosive changes, which will be correlated with the presence and severity of synovial pannus in that same joint. Analysis will also be performed to see if there is a correlation with serum urate levels. A sub-study will be performed assessing the effect of aggressive serum urate lowering therapy (specifically with febuxostat [Uloric]) on this chronic inflammation; i.e. synovial pannus.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01112982
|United States, Florida|
|University of South Florida Medical Clinics|
|Tampa, Florida, United States, 33612-4742|
|Study Director:||Ernesto J Rodriguez, MD||University Of South Florida, Department of Rheumatology|
|Principal Investigator:||John D Carter, MD||University Of South Florida, Department of Rheumatology|