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

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ClinicalTrials.gov Identifier: NCT01112982
Recruitment Status : Completed
First Posted : April 29, 2010
Results First Posted : August 7, 2019
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
University of South Florida

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.

Condition or disease Intervention/treatment Phase
Gout Other: Magnetic Resonance Imaging Drug: Febuxostat Drug: Colchicine Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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.
Study Start Date : May 2010
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout

Arm Intervention/treatment
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 Name: 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 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

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 Name: 3 Tesla Magnetic Resonance Imaging




Primary Outcome Measures :
  1. Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline. [ Time Frame: MRI and baseline uric acid level will be performed upon enrollment in the study. ]
    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 :
  1. Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric). [ Time Frame: Upon enrollment into study, and at month 9. ]
    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.

  2. Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. [ Time Frame: Upon enrollment into study ]
    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.

  3. Mean Serum Urate Levels for Previous 2 Years at Baseline. [ Time Frame: previous 2 years upon enrollment into study ]
    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.

  4. The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging [ Time Frame: Upon enrollment into study at screening. ]
    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).

  5. 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. [ Time Frame: Upon enrollment into study ]
    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.

  6. High-sensitivity C-Reactive Protein Concentrations [ Time Frame: Upon enrollment into study at screening. ]
    The concentration of serum high-sensitivity C-Reactive Protein at enrollment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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]

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01112982


Locations
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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
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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

Additional Information:
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Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT01112982     History of Changes
Other Study ID Numbers: Pro00000136
First Posted: April 29, 2010    Key Record Dates
Results First Posted: August 7, 2019
Last Update Posted: August 7, 2019
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of South Florida:
Gout
Synovial pannus
Magnetic resonance imaging
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes
Colchicine
Febuxostat
Uric Acid
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antioxidants
Protective Agents
Physiological Effects of Drugs