Assessing the Role of the NLRP3 Inflammasome in Intercritical Gout

Study Overview
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Brief Summary
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Gout is an autoinflammatory disease characterized by flares of painful joint inflammation. This inflammation occurs in response to uric acid that crystallizes. After a gout attack, patients usually enter a period that is accompanied by low grade inflammation but is otherwise relatively asymptomatic. Gout is typically associated with certain markers, and this study is going describe specific markers in patients that are in between gout attacks. Research has been focused on studying this phase between gout attacks in hopes to manage and prevent the onset of future gout attacks. Biopsies will be taken from the affected joint and blood will be drawn from patients who are currently in between gout attacks. This work will provide important information regarding how crystals in the joint lining are associated with chronic inflammation in the periods between gout attacks. Moreover, this study will identify novel biomarkers that may be useful in determining the severity of disease activity through a blood test.

Official Title
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Assessing the Role of the NLRP3 Inflammasome in Driving Inflammation in Affected Joints of Patients With Intercritical Gout

Conditions
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Gout

Intervention / Treatment
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* Procedure: Joint Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with gout diagnosed by a Rheumatologist. patients with a history of at least two gout attacks in the target joint Patients with a target joint amenable to biopsy. Target joint defined as: Joint that has been affected by acute gout attack at least twice in the 12 months prior to enrollment. Ultrasound finds grade 2 gray-scale synovitis in joint. Joint is amenable to biopsy. At the time of enrollment, the joint is without signs of acute inflammation: redness, swelling, and severe pain (>7/10). Exclusion Criteria: Patients on anti-coagulation therapy. Patients with an active infection. Tophus present at the biopsy site. Target joint with signs of acute gout attack (pain >7/10, redness, warmth) Known chondrocalcinosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with Gout<br>This arm will be getting a biopsy as well as a blood draw | Procedure: Joint Biopsy<br>* a synovial biopsy of a joint that has been affected by a gout attack<br>|
| Controls<br>These individuals will not be getting a joint biopsy and will just get a blood draw | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NLRP3 Inflammasome Role in Driving Inflammation in Intercritical Gout | To investigate the role of the NLRP3 inflammasome in driving inflammation in intercritical gout. Specifically, this will be accomplished via measuring caspase-1 activity as a marker of inflammasome activity. We will measure the % of patients who show a %positivity (physiological parameter) of caspase-1 activity. | Up to 2 months | 
| IL-1B Role in Driving Inflammation in Intercritical Gout | Examine the role of IL-1b in driving inflammation within intercritical gout via the measurement of IL-1b levels. IL-1b concentration levels (physiological parameter) will be measured in ng/ml. | Up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microcrystal Correlation | Correlate NLRP3 activity with the presence of microcrystals in the synovium | Up to 2 months | 
| Immune Cell Infiltration in the Inflamed Joint Correlation | Correlate NLRP3 activity with the presence of infiltration of immune cells in the inflamed joint as determined by flow cytometry and cytology | Up to 2 months | 
| Uric Acid Levels Correlation | Correlate NLRP3 activity with the concentration of uric acid levels in mg/dL | Up to 2 months |