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

Gout Clinical Trial

Official title:

Shifting the Paradigm of Gout: An Assessment of Chronic Synovial-Based Inflammation and Its Role With Serum Urate Levels.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01112982
• Other study ID #: Pro00000136
• Status: Completed
• Phase: Phase 4
• Start date: May 2010
• Est. completion date: December 2014

Study information

• Verified date: March 2017
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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]

Related Conditions & MeSH terms

• Gout
• Inflammation

Intervention

Other:
• Magnetic Resonance Imaging
An Magnetic Resonance Imaging (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).

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.
• 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.

Locations

Country	Name	City	State
United States	University of South Florida Medical Clinics	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of South Florida	Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	High-sensitivity C-Reactive Protein Concentrations	The concentration of serum high-sensitivity C-Reactive Protein at enrollment.	Upon enrollment into study at screening.

External Links

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