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

Shifting the Paradigm of Gout: 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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Other: Magnetic Resonance Imaging; Drug: Febuxostat; Drug: Colchicine

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612-4742
      • University of South Florida Medical Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Febuxostat Sub-Study; 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).	Other: Magnetic Resonance Imaging; An Magnetic Resonance Imaging (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).; Other Names: 3 Tesla Magnetic Resonance Imaging; 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 Names: 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 Names: Colcrys
Other: MRI of index joint; 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).	Other: Magnetic Resonance Imaging; An Magnetic Resonance Imaging (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).; Other Names: 3 Tesla Magnetic Resonance Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline.	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.	MRI and baseline uric acid level will be performed upon enrollment in the study.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric).	A sub-study in a subgroup of patients will analyze the Number and Percentage of Substudy Participants for whom the Severity of Synovial Pannus was Significantly Reduced After 9 Months of Treatment with Febuxostat (Uloric) in the "index joint" by comparing the baseline MRI with a repeat MRI of the same joint.	Upon enrollment into study, and at month 9.
Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels.	Number of Participants with Other Characteristic Findings of Gout on these MRI's. These include erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema, and soft tissue edema. These secondary endpoints will also be summed with patients' serum urate levels.	Upon enrollment into study
Mean Serum Urate Levels for Previous 2 Years at Baseline.	Determine if there is a correlation between the prevalence and severity of synovial pannus in the "index joint" with the patients' mean serum urate level from the previous 2 years at baseline.	previous 2 years upon enrollment into study
The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging	Determine if the Number of Participants Prevalence and Severity of Synovial Pannus in the "Index Joint" with the patient's serum high-sensitivity C-Reactive Protein on the same day as the Magnetic Resonance Imaging. The Magnetic Resonance Imaging will be assessed for the severity of synovial pannus, which is graded on a scale of 1 to 6 (with 6 being the most severe).	Upon enrollment into study at screening.
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.	Baseline radiographs of the "index" joint will also be obtained on the same day as their MRI and assessed for the presence or absence of erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema, or soft tissue edema. This will be correlated with the presence and severity of synovial pannus in that same joint. The analysis will also be performed to see if there is a correlation with serum urate levels and the presence of erosions on their plain radiograph.	Upon enrollment into study
High-sensitivity C-Reactive Protein Concentrations	The concentration of serum high-sensitivity C-Reactive Protein at enrollment.	Upon enrollment into study at screening.

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: 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

Publications and helpful links

Helpful Links

• Medline Plus: Gout
• Medline Plus: Febuxostat
• Medline Plus: Colchicine
• Medline Plus: MRI

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: April 28, 2010
• First Posted (Estimate): April 29, 2010

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: July 18, 2019
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Gout; Synovial pannus
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine; Febuxostat
• Other Study ID Numbers: Pro00000136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No