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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT01112982
First received: April 27, 2010
Last updated: December 11, 2013
Last verified: December 2013
  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.

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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: December 2014
Estimated Primary Completion Date: December 2014 (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
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]
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01112982

Locations
United States, Florida
University of South Florida Medical Clinics
Tampa, Florida, United States, 33612-4742
Sponsors and Collaborators
University of South Florida
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
  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: December 11, 2013
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 July 24, 2014