Gout
Conditions
Keywords
Gout, Synovial pannus, Magnetic resonance imaging
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.
Interventions
OTHERMagnetic Resonance Imaging
An Magnetic Resonance Imaging (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).
DRUGFebuxostat
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.
DRUGColchicine
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.
Sponsors
Takeda Pharmaceuticals North America, Inc.
University of South Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[substudy subjects only\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline. | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | 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. |
| Mean Serum Urate Levels for Previous 2 Years at Baseline. | 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. |
| Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric). | 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. |
| 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. | 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. |
| High-sensitivity C-Reactive Protein Concentrations | Upon enrollment into study at screening. | The concentration of serum high-sensitivity C-Reactive Protein at enrollment. |
| The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MRI of Index Joint 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.
Magnetic Resonance Imaging: An MRI (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images).
Plain Radiographs: Plain radiographs of index joint will be obtained and reviewed by two independent readers (radiologists) | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | exceeded weight limit to complete MRI | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MRI of Index Joint |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants |
| Age, Continuous | 56.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 59 Participants |
| Region of Enrollment United States | 72 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 72 |
| other Total, other adverse events | 8 / 72 |
| serious Total, serious adverse events | 1 / 72 |
Outcome results
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.
Time frame: MRI and baseline uric acid level will be performed upon enrollment in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MRI of Index Joint | Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline. | 63 Participants |
Comparison: Presence of synovial pannus and the serum urate level.p-value: 0.34t-test, 2 sided
Secondary
High-sensitivity C-Reactive Protein Concentrations
The concentration of serum high-sensitivity C-Reactive Protein at enrollment.
Time frame: Upon enrollment into study at screening.
Population: Serum High-Sensitivity C-Reactive Protein
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MRI of Index Joint | High-sensitivity C-Reactive Protein Concentrations | 0.52 mg/dL | Standard Deviation 0.84 |
| Febuxostat Sub-Study | High-sensitivity C-Reactive Protein Concentrations | 0.37 mg/dL | Standard Deviation 0.4 |
p-value: 0.32t-test, 1 sided
p-value: 0.99t-test, 1 sided
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.
Time frame: previous 2 years upon enrollment into study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MRI of Index Joint | Mean Serum Urate Levels for Previous 2 Years at Baseline. | 7.93 mg/dL | Standard Deviation 2.13 |
p-value: 0.73t-test, 1 sided
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.
Time frame: Upon enrollment into study, and at month 9.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MRI of Index Joint | Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric). | 25 Participants |
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.
Time frame: Upon enrollment into study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Erosive Changes | 31 Participants |
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Intraosseous tophi | 25 Participants |
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Soft tissue tophi | 11 Participants |
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Joint effusion | 14 Participants |
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Bone marrow edema | 40 Participants |
| MRI of Index Joint | Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels. | Soft tissue edema | 28 Participants |
Comparison: The Severity of Synovial Pannus and the Serum Urate level.p-value: 0.73t-test, 1 sided
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.
Time frame: Upon enrollment into study
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| MRI of Index Joint | 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. | Erosive Changes | Presence | 31 Participants |
| MRI of Index Joint | 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. | Erosive Changes | Absence | 41 Participants |
| MRI of Index Joint | 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. | Serum urate levels ≤6.8mg/dL | Presence | 24 Participants |
| MRI of Index Joint | 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. | Serum urate levels ≤6.8mg/dL | Absence | 48 Participants |
| MRI of Index Joint | 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. | Intraosseous Tophi | Presence | 25 Participants |
| MRI of Index Joint | 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. | Intraosseous Tophi | Absence | 47 Participants |
| MRI of Index Joint | 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. | Soft Tissue Tophi | Presence | 11 Participants |
| MRI of Index Joint | 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. | Soft Tissue Tophi | Absence | 61 Participants |
| MRI of Index Joint | 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. | Joint Effusion | Presence | 14 Participants |
| MRI of Index Joint | 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. | Joint Effusion | Absence | 58 Participants |
| MRI of Index Joint | 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. | Bone Marrow Edema | Presence | 40 Participants |
| MRI of Index Joint | 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. | Bone Marrow Edema | Absence | 32 Participants |
| MRI of Index Joint | 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. | Soft Tissue Edema | Presence | 28 Participants |
| MRI of Index Joint | 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. | Soft Tissue Edema | Absence | 44 Participants |
Comparison: The absence of erosive changes.p-value: 0.09t-test, 2 sided
p-value: 0.33t-test, 2 sided
p-value: 0.09t-test, 2 sided
p-value: 0.31t-test, 2 sided
p-value: 0.25t-test, 2 sided
p-value: 0.14t-test, 2 sided
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).
Time frame: Upon enrollment into study at screening.
Population: Severity of Synovial Pannus in the Index Joint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MRI of Index Joint | The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging | 2.99 units on a scale | Standard Deviation 1.3 |
| Febuxostat Sub-Study | The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging | 3.42 units on a scale | Standard Deviation 1.3 |
p-value: 0.32t-test, 1 sided