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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

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition Gout
Interventions Other: Magnetic Resonance Imaging
Drug: Febuxostat
Drug: Colchicine
Enrollment 74
Recruitment Details  
Pre-assignment Details  
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description

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)

Period Title: Overall Study
Started 74
Completed 72
Not Completed 2
Reason Not Completed
Withdrawal by Subject             1
exceeded weight limit to complete MRI             1
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description

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)

Overall Number of Baseline Participants 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
<=18 years
0
   0.0%
Between 18 and 65 years
67
  93.1%
>=65 years
5
   6.9%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 72 participants
56.4
(28 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
Female
7
   9.7%
Male
65
  90.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
Hispanic or Latino
9
  12.5%
Not Hispanic or Latino
60
  83.3%
Unknown or Not Reported
3
   4.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
10
  13.9%
White
59
  81.9%
More than one race
0
   0.0%
Unknown or Not Reported
3
   4.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 72 participants
72
 100.0%
1.Primary Outcome
Title Number and Percentage of Participants With Evidence of Chronic Ongoing Synovial-Based Inflammatory Disease at Baseline.
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description:

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)

Overall Number of Participants Analyzed 72
Measure Type: Count of Participants
Unit of Measure: Participants
63
  87.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments Presence of synovial pannus and the serum urate level.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Number and Percentage of Substudy Participants for Whom the Severity of Synovial Pannus Was Significantly Reduced After 9 Months of Treatment With Febuxostat (Uloric).
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Febuxostat Sub-Study
Hide Arm/Group Description:
The primary endpoint of this sub-study was to determine if a nine month course of aggressive serum ULT in patients with gout significantly affects the severity of synovial pannus in the index joint as determined by comparing the baseline and month 9 MRI’s using the aforementioned grading scale. Secondary endpoints included an assessment of significant change of the subjects’ serum CRP and estimated Glomerular Filtration Rate (eGFR) from baseline to month 9. Other endpoints included assessing for significant change of erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema/lesions, and soft tissue edema on the MRI from baseline to month 9.
Overall Number of Participants Analyzed 32
Measure Type: Count of Participants
Unit of Measure: Participants
25
  78.1%
3.Secondary Outcome
Title Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description:

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)

Overall Number of Participants Analyzed 72
Measure Type: Count of Participants
Unit of Measure: Participants
Erosive Changes
31
  43.1%
Intraosseous tophi
25
  34.7%
Soft tissue tophi
11
  15.3%
Joint effusion
14
  19.4%
Bone marrow edema
40
  55.6%
Soft tissue edema
28
  38.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments The Severity of Synovial Pannus and the Serum Urate level.
Type of Statistical Test Other
Comments Spearman Correlation Coefficient
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
4.Secondary Outcome
Title Mean Serum Urate Levels for Previous 2 Years at Baseline.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description:

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.

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

Overall Number of Participants Analyzed 72
Mean (Standard Deviation)
Unit of Measure: mg/dL
7.93  (2.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments correlation between severity of synovial pannus and the serum urate level.
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
5.Secondary Outcome
Title The Severity of Synovial Pannus the Day of Serum High-sensitivity C-Reactive Protein and Magnetic Resonance Imaging
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Severity of Synovial Pannus in the "Index Joint"
Arm/Group Title MRI of Index Joint Febuxostat Sub-Study
Hide Arm/Group Description:

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.

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

The primary endpoint of this sub-study was to determine if a nine month course of aggressive serum ULT in patients with gout significantly affects the severity of synovial pannus in the index joint as determined by comparing the baseline and month 9 MRI’s using the aforementioned grading scale. Secondary endpoints included an assessment of significant change of the subjects’ serum CRP and estimated Glomerular Filtration Rate (eGFR) from baseline to month 9. Other endpoints included assessing for significant change of erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema/lesions, and soft tissue edema on the MRI from baseline to month 9.
Overall Number of Participants Analyzed 72 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.99  (1.3) 3.42  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments The presence of synovial pannus in the “index joint”.
Method t-test, 1 sided
Comments [Not Specified]
6.Secondary Outcome
Title 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.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description:

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.

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

Overall Number of Participants Analyzed 72
Measure Type: Count of Participants
Unit of Measure: Participants
Erosive Changes Presence
31
  43.1%
Absence
41
  56.9%
Serum urate levels ≤6.8mg/dL Presence
24
  33.3%
Absence
48
  66.7%
Intraosseous Tophi Presence
25
  34.7%
Absence
47
  65.3%
Soft Tissue Tophi Presence
11
  15.3%
Absence
61
  84.7%
Joint Effusion Presence
14
  19.4%
Absence
58
  80.6%
Bone Marrow Edema Presence
40
  55.6%
Absence
32
  44.4%
Soft Tissue Edema Presence
28
  38.9%
Absence
44
  61.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments The absence of erosive changes.
Type of Statistical Test Other
Comments Kappa Coefficient
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments the absence of Intraosseous Tophi.
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments The absence of Soft Tissue Tophi
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments The absence of Joint Effusion.
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments The absence of Bone Marrow Edema.
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments The absence of Soft Tissue Edema.
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title High-sensitivity C-Reactive Protein Concentrations
Hide Description The concentration of serum high-sensitivity C-Reactive Protein at enrollment.
Time Frame Upon enrollment into study at screening.
Hide Outcome Measure Data
Hide Analysis Population Description
Serum High-Sensitivity C-Reactive Protein
Arm/Group Title MRI of Index Joint Febuxostat Sub-Study
Hide Arm/Group Description:

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.

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

The primary endpoint of this sub-study was to determine if a nine month course of aggressive serum ULT in patients with gout significantly affects the severity of synovial pannus in the index joint as determined by comparing the baseline and month 9 MRI’s using the aforementioned grading scale. Secondary endpoints included an assessment of significant change of the subjects’ serum CRP and estimated Glomerular Filtration Rate (eGFR) from baseline to month 9. Other endpoints included assessing for significant change of erosive changes, intraosseous tophi, soft tissue tophi, joint effusion, bone marrow edema/lesions, and soft tissue edema on the MRI from baseline to month 9.
Overall Number of Participants Analyzed 72 25
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.52  (0.84) 0.37  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments The Presence of synovial Pannus in the "index joint".
Method t-test, 1 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MRI of Index Joint
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments The Severity of Synovial Pannus in the "index joint".
Method t-test, 1 sided
Comments [Not Specified]
Time Frame At screening, baseline, week 2, month 1, month 3, month 6, and month 9 adverse events were collected on 72 study participants.
Adverse Event Reporting Description All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were monitored/assessed.
 
Arm/Group Title MRI of Index Joint
Hide Arm/Group Description

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)

All-Cause Mortality
MRI of Index Joint
Affected / at Risk (%)
Total   0/72 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
MRI of Index Joint
Affected / at Risk (%) # Events
Total   1/72 (1.39%)    
Cardiac disorders   
exacerbation of congestive heart failure * 1 [1]  1/72 (1.39%)  1
1
Term from vocabulary, MedDRA (10.0)
*
Indicates events were collected by non-systematic assessment
[1]
exacerbation of congestive heart failure requiring hospitalization.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
MRI of Index Joint
Affected / at Risk (%) # Events
Total   8/72 (11.11%)    
Cardiac disorders   
thrombocytopenia * 1 [1]  1/72 (1.39%)  1
Gastrointestinal disorders   
mild nausea * 1 [2]  2/72 (2.78%)  2
Hepatobiliary disorders   
increased liver function tests * 1 [3]  8/72 (11.11%)  8
1
Term from vocabulary, MedDRA (10.0)
*
Indicates events were collected by non-systematic assessment
[1]
mild thrombocytopenia without complication.
[2]
experienced mild nausea that resolved with supportive care.
[3]
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John Carter, M.D
Organization: University of South Florida
Phone: 813-974-2473
EMail: mpatelli@health.usf.edu
Layout table for additonal information
Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT01112982     History of Changes
Other Study ID Numbers: Pro00000136
First Submitted: April 27, 2010
First Posted: April 29, 2010
Results First Submitted: March 27, 2017
Results First Posted: August 7, 2019
Last Update Posted: August 7, 2019