An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Gout |
Other: Magnetic Resonance Imaging Other: Plain Radiographs Drug: Febuxostat Drug: Colchicine |
Phase 4 |
| Study Type: | Interventional |
| 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.
| Estimated Enrollment: | 76 |
| Study Start Date: | May 2010 |
| Estimated Study Completion Date: | March 2013 |
| Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
MRI Arm
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 MRI
Other: 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).
|
Drug: Febuxostat
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: Uloric
Drug: 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
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age > or = 18 - Open ended to both males and females.
- Have a known history of gout diagnosed by current or previous documentation of intracellular MSU crystals in synovial fluid, a tophus proved to contain MSU crystals, or at least six of the twelve ACR diagnostic criteria for gout (see appendix with the 12 diagnostic criteria of gout).
- English of Spanish speaking
- Able to give informed consent
Exclusion Criteria:
- Age < 18.
- Unable to give informed consent.
- Do not speak or write in English or Spanish.
- History of any other inflammatory arthritis.
- History of another crystal induced arthritis.
- Serum creatinine >1.8 mg/dL
- Patients taking oral corticosteroids (any dose) [or within 4 weeks]
- Parenteral or intraarticular corticosteroids within 6 weeks
- Allergy to gadolinium contrast dye
- Any contraindication to receiving a MRI
- Pregnant women
- Allergy to febuxostat (Uloric) or colchicine [substudy subjects only]
Contacts and Locations| 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 |
More Information
Additional Information:
No publications provided
| Responsible Party: | University of South Florida |
| ClinicalTrials.gov Identifier: | NCT01112982 History of Changes |
| Other Study ID Numbers: | Pro00000136 |
| Study First Received: | April 27, 2010 |
| Last Updated: | July 16, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of South Florida:
|
Gout Synovial pannus Magnetic resonance imaging |
Additional relevant MeSH terms:
|
Gout Inflammation Arthritis Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Purine-Pyrimidine Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Pathologic Processes |
Colchicine Febuxostat Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Gout Suppressants Antirheumatic Agents Therapeutic Uses Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 23, 2013