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

NCT01112982 | Completed Phase 4 Results

• 1 other identifier: Pro00000136
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Gout

Keywords

Gout; Synovial pannus; Magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (6)

• 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.

• Number of Participants With Other Characteristic Findings of Gout on MRI's Correlated With Serum Urate Levels.

  Upon enrollment into study

• Mean Serum Urate Levels for 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

  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.

  Upon enrollment into study

Study Arms (2)

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).

Other: Magnetic Resonance Imaging; Drug: Febuxostat; Drug: Colchicine

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).

Other: Magnetic Resonance Imaging

Interventions

Magnetic Resonance Imaging OTHER

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

Also known as: 3 Tesla Magnetic Resonance Imaging

Febuxostat Sub-Study; MRI of index joint

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.

Also known as: Uloric

Febuxostat Sub-Study

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.

Also known as: Colcrys

Febuxostat Sub-Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> or = 18 - Open ended to both males and females.
• 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).
• English of Spanish speaking
• Able to give informed consent

You may not qualify if:

• Age \< 18.
• Unable to give informed consent.
• Do not speak or write in English or Spanish.
• History of any other inflammatory arthritis.
• History of another crystal induced arthritis.
• Serum creatinine \>1.8 mg/dL
• Patients taking oral corticosteroids (any dose) \[or within 4 weeks\]
• Parenteral or intraarticular corticosteroids within 6 weeks
• Allergy to gadolinium contrast dye
• Any contraindication to receiving a MRI
• Pregnant women
• Allergy to febuxostat (Uloric) or colchicine \[substudy subjects only\]

Sponsors & Collaborators

• University of South Florida: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

University of South Florida Medical Clinics

Tampa, Florida, 33612-4742, United States

Location

Related Links

• Medline Plus: Gout
• Medline Plus: Febuxostat
• Medline Plus: Colchicine
• Medline Plus: MRI

MeSH Terms

Conditions

Gout

Interventions

Magnetic Resonance Spectroscopy; Febuxostat; Colchicine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids

Limitations and Caveats

two subjects who did not complete the entire protocol, one exceeded the weight limit to complete the MRI, and the other withdrew consent.

Results Point of Contact

• Title: John Carter, M.D
• Organization: University of South Florida

mpatelli@health.usf.edu

813-974-2473

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: April 29, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 7, 2019
• Results First Posted: August 7, 2019

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)