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| Name | Class |
|---|---|
| Takeda Pharmaceuticals North America, Inc. | INDUSTRY |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Febuxostat Sub-Study | Other | 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). |
|
| MRI of index joint | Other | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Magnetic Resonance Imaging | Other | An Magnetic Resonance Imaging (with and without gadolinium contrast) of index joint will be performed (T1, T2, and STIR images). |
|
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ernesto J Rodriguez, MD | University Of South Florida, Department of Rheumatology | Study Director |
| John D Carter, MD | University Of South Florida, Department of Rheumatology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of South Florida Medical Clinics | Tampa | Florida | 33612-4742 | United States |
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| Label | URL |
|---|---|
| Medline Plus: Gout | View source |
| Medline Plus: Febuxostat | View source |
| Medline Plus: Colchicine |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | MRI and baseline uric acid level will be performed upon enrollment in the study. |
|
At screening, baseline, week 2, month 1, month 3, month 6, and month 9 adverse events were collected on 72 study participants.
All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were monitored/assessed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| exacerbation of congestive heart failure | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment | exacerbation of congestive heart failure requiring hospitalization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| increased liver function tests | Hepatobiliary disorders | MedDRA (10.0) | Non-systematic Assessment | increased liver function tests (LFT). 8/25 (32%) subjects experienced some degree of LFT elevation during the study, but only 1 (4%) subject experienced increased LFTs of greater than two times the upper limit of normal. |
two subjects who did not complete the entire protocol, one exceeded the weight limit to complete the MRI, and the other withdrew consent.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Carter, M.D | University of South Florida | 813-974-2473 | mpatelli@health.usf.edu |
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| ID | Term |
|---|---|
| D006073 | Gout |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
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| ID | Term |
|---|---|
| D009682 | Magnetic Resonance Spectroscopy |
| D000069465 | Febuxostat |
| D003078 | Colchicine |
| ID | Term |
|---|---|
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D013844 | Thiazoles |
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|
| Febuxostat | Drug | 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. |
|
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| Colchicine | Drug | 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. |
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| 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. |
| Medline Plus: MRI | View source |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
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|
|
| 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 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. | Posted | Mean | Standard Deviation | mg/dL | 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). | Severity of Synovial Pannus in the "Index Joint" | Posted | Mean | Standard Deviation | units on a scale | Upon enrollment into study at screening. |
|
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| 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. | Posted | Count of Participants | Participants | Upon enrollment into study |
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| Secondary | High-sensitivity C-Reactive Protein Concentrations | The concentration of serum high-sensitivity C-Reactive Protein at enrollment. | Serum High-Sensitivity C-Reactive Protein | Posted | Mean | Standard Deviation | mg/dL | Upon enrollment into study at screening. |
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|
| 0 |
| 72 |
| 1 |
| 72 |
| 8 |
| 72 |
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| thrombocytopenia | Cardiac disorders | MedDRA (10.0) | Non-systematic Assessment | mild thrombocytopenia without complication. |
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| mild nausea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment | experienced mild nausea that resolved with supportive care. |
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| D012216 |
| Rheumatic Diseases |
| D011686 | Purine-Pyrimidine Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D013457 |
| Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000470 | Alkaloids |
| Title | Measurements |
|---|---|
|
| Joint effusion |
|
| Bone marrow edema |
|
| Soft tissue edema |
|
| Absence |
|
| Intraosseous Tophi |
|
| Soft Tissue Tophi |
|
| Joint Effusion |
|
| Bone Marrow Edema |
|
| Soft Tissue Edema |
|
| Other |
the absence of Intraosseous Tophi. |
| t-test, 2 sided | 0.09 | Other | The absence of Soft Tissue Tophi |
| t-test, 2 sided | 0.31 | Other | The absence of Joint Effusion. |
| t-test, 2 sided | 0.25 | Other | The absence of Bone Marrow Edema. |
| t-test, 2 sided | 0.14 | Other | The absence of Soft Tissue Edema. |
The Severity of Synovial Pannus in the "index joint".
| Other |