An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.

University of South Florida

Status and phase: Completed; Phase 4

Conditions: Gout

Treatments: Drug: Febuxostat; Other: Magnetic Resonance Imaging; Drug: Colchicine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01112982

Pro00000136

Details and patient eligibility

About

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.

Full 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.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age > or = 18 - Open ended to both males and females.
2. 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).
3. English of Spanish speaking
4. Able to give informed consent

Exclusion criteria

1. Age < 18.
2. Unable to give informed consent.
3. Do not speak or write in English or Spanish.
4. History of any other inflammatory arthritis.
5. History of another crystal induced arthritis.
6. Serum creatinine >1.8 mg/dL
7. Patients taking oral corticosteroids (any dose) [or within 4 weeks]
8. Parenteral or intraarticular corticosteroids within 6 weeks
9. Allergy to gadolinium contrast dye
10. Any contraindication to receiving a MRI
11. Pregnant women
12. Allergy to febuxostat (Uloric) or colchicine [substudy subjects only]

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

Febuxostat Sub-Study

Other group

Description:

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. Magnetic Resonance Imaging (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).

Treatment:

Drug: Colchicine

Other: Magnetic Resonance Imaging

Drug: Febuxostat

MRI of index joint

Other group

Description:

To analyze synovial pannus in the Magnetic Resonance Imaging (with and without gadolinium) of the "index joint" on Subjects not currently on any urate-lowering therapy, or on a serum urate lowering drug other than febuxostat (Uloric).

Treatment:

Other: Magnetic Resonance Imaging