Clinical trial NCT01112982: An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
Official title: Shifting the Paradigm of Gout: An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gout
Keywords: Gout
Synovial pannus
Magnetic resonance imaging
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2010-04-29
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 criteria: 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 \[substudy subjects only\]

Primary outcomes:
measure: Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline.
timeFrame: MRI and baseline uric acid level will be performed upon enrollment in the study.
Secondary outcomes:
measure: Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric).
timeFrame: Upon enrollment into study, and at month 9.
measure: Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels.
timeFrame: Upon enrollment into study
measure: Mean Serum Urate Levels for Previous 2 Years at Baseline.
timeFrame: previous 2 years upon enrollment into study
measure: The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging
timeFrame: Upon enrollment into study at screening.
measure: Presence or Absence of Erosive Changes on Baseline Radiographs of the "Index" Joint Correlated With the Presence and Severity of Synovial Pannus Correlation With Serum Urate Levels and the Presence of Erosions on Their Plain Radiograph.
timeFrame: Upon enrollment into study
measure: High-sensitivity C-Reactive Protein Concentrations
timeFrame: Upon enrollment into study at screening.
Other outcomes:
Locations:
city: Tampa
country: United States
facility: University of South Florida Medical Clinics
state: Florida
Study officials:
affiliation: University Of South Florida, Department of Rheumatology
name: Ernesto J Rodriguez, MD
role: STUDY_DIRECTOR
affiliation: University Of South Florida, Department of Rheumatology
name: John D Carter, MD
role: PRINCIPAL_INVESTIGATOR
References: