Assessing the Role of the NLRP3 Inflammasome in Intercritical Gout
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Individuals with Gout This arm will be getting a biopsy as well as a blood draw |
Procedure: Joint Biopsy
a synovial biopsy of a joint that has been affected by a gout attack
|
Controls These individuals will not be getting a joint biopsy and will just get a blood draw |
Outcome Measures
Primary Outcome Measures
- NLRP3 Inflammasome Role in Driving Inflammation in Intercritical Gout [Up to 2 months]
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.
- IL-1B Role in Driving Inflammation in Intercritical Gout [Up to 2 months]
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.
Secondary Outcome Measures
- Microcrystal Correlation [Up to 2 months]
Correlate NLRP3 activity with the presence of microcrystals in the synovium
- Immune Cell Infiltration in the Inflamed Joint Correlation [Up to 2 months]
Correlate NLRP3 activity with the presence of infiltration of immune cells in the inflamed joint as determined by flow cytometry and cytology
- Uric Acid Levels Correlation [Up to 2 months]
Correlate NLRP3 activity with the concentration of uric acid levels in mg/dL
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Attune Health Research Inc. | Beverly Hills | California | United States | 90211 |
Sponsors and Collaborators
- Attune Health Research, Inc.
- Horizon Pharma Ireland, Ltd., Dublin Ireland
Investigators
- Principal Investigator: Swamy Venuturupalli, MD, Attune Health
Study Documents (Full-Text)
None provided.More Information
Publications
- Agudelo CA, Schumacher HR. The synovitis of acute gouty arthritis. A light and electron microscopic study. Hum Pathol. 1973 Jun;4(2):265-79.
- Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, Soriani FM, Silveira TN, Cunha LD, Zamboni DS, Quesniaux V, Peres RS, Cunha TM, Cunha FQ, Ryffel B, Souza DG, Teixeira MM. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum. 2012 Feb;64(2):474-84. doi: 10.1002/art.33355.
- Andersen M, Ellegaard K, Hebsgaard JB, Christensen R, Torp-Pedersen S, Kvist PH, Søe N, Rømer J, Vendel N, Bartels EM, Danneskiold-Samsøe B, Bliddal H. Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study. Ann Rheum Dis. 2014 Apr;73(4):678-83. doi: 10.1136/annrheumdis-2012-202669. Epub 2013 Mar 8.
- Burns CM, Wortmann RL. Latest evidence on gout management: what the clinician needs to know. Ther Adv Chronic Dis. 2012 Nov;3(6):271-86. doi: 10.1177/2040622312462056.
- Carter JD, Patelli M, Anderson SR, Prakash N, Rodriquez EJ, Bateman H, Sterrett A, Valeriano J, Ricca LR. An MRI assessment of chronic synovial-based inflammation in gout and its correlation with serum urate levels. Clin Rheumatol. 2015 Feb;34(2):345-51. doi: 10.1007/s10067-014-2644-9. Epub 2014 May 7.
- Goldenberg DL, Cohen AS. Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease. Medicine (Baltimore). 1978 May;57(3):239-52.
- Gonçalves B, Ambrosio C, Serra S, Alves F, Gil-Agostinho A, Caseiro-Alves F. US-guided interventional joint procedures in patients with rheumatic diseases--when and how we do it? Eur J Radiol. 2011 Sep;79(3):407-14. doi: 10.1016/j.ejrad.2010.04.001. Epub 2010 Jun 4.
- Grainger R, McLaughlin RJ, Harrison AA, Harper JL. Hyperuricaemia elevates circulating CCL2 levels and primes monocyte trafficking in subjects with inter-critical gout. Rheumatology (Oxford). 2013 Jun;52(6):1018-21. doi: 10.1093/rheumatology/kes326. Epub 2012 Nov 30.
- Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015 Jul;21(7):677-87. doi: 10.1038/nm.3893. Epub 2015 Jun 29. Review.
- Hirsch JD, Terkeltaub R, Khanna D, Singh J, Sarkin A, Shieh M, Kavanaugh A, Lee SJ. Gout disease-specific quality of life and the association with gout characteristics. Patient Relat Outcome Meas. 2010 Mar 1;2010:1-8.
- Humby F, Kelly S, Hands R, Rocher V, DiCicco M, Ng N, Zou L, Bugatti S, Manzo A, Caporali R, Montecucco C, Bombardieri M, Pitzalis C. Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy: recommendations for application to clinical trials. Arthritis Rheumatol. 2015 Oct;67(10):2601-10. doi: 10.1002/art.39235.
- Jarrah AA, Tarzami ST. The duality of chemokines in heart failure. Expert Rev Clin Immunol. 2015 Apr;11(4):523-36. doi: 10.1586/1744666X.2015.1024658. Epub 2015 Mar 12. Review.
- Kelly S, Humby F, Filer A, Ng N, Di Cicco M, Hands RE, Rocher V, Bombardieri M, D'Agostino MA, McInnes IB, Buckley CD, Taylor PC, Pitzalis C. Ultrasound-guided synovial biopsy: a safe, well-tolerated and reliable technique for obtaining high-quality synovial tissue from both large and small joints in early arthritis patients. Ann Rheum Dis. 2015 Mar;74(3):611-7. doi: 10.1136/annrheumdis-2013-204603. Epub 2013 Dec 13.
- Kingsbury SR, Conaghan PG, McDermott MF. The role of the NLRP3 inflammasome in gout. J Inflamm Res. 2011;4:39-49. doi: 10.2147/JIR.S11330. Epub 2011 Mar 13.
- Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006 Aug;54(8):2688-96.
- Kuo CF, See LC, Luo SF, Ko YS, Lin YS, Hwang JS, Lin CM, Chen HW, Yu KH. Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology (Oxford). 2010 Jan;49(1):141-6. doi: 10.1093/rheumatology/kep364. Epub 2009 Nov 20.
- Landis RC, Haskard DO. Pathogenesis of crystal-induced inflammation. Curr Rheumatol Rep. 2001 Feb;3(1):36-41. Review.
- Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, Liang MH, Pillemer SR, Steen VD, Wolfe F. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998 May;41(5):778-99.
- Najm A, Orr C, Heymann MF, Bart G, Veale DJ, Le Goff B. Success Rate and Utility of Ultrasound-guided Synovial Biopsies in Clinical Practice. J Rheumatol. 2016 Dec;43(12):2113-2119. Epub 2016 Oct 15.
- Neogi T, Hunter DJ, Chaisson CE, Allensworth-Davies D, Zhang Y. Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study. J Rheumatol. 2006 Jan;33(1):104-9. Epub 2005 Nov 1.
- Pascual E. Persistence of monosodium urate crystals and low-grade inflammation in the synovial fluid of patients with untreated gout. Arthritis Rheum. 1991 Feb;34(2):141-5.
- Ragab G, Elshahaly M, Bardin T. Gout: An old disease in new perspective - A review. J Adv Res. 2017 Sep;8(5):495-511. doi: 10.1016/j.jare.2017.04.008. Epub 2017 May 10. Review.
- Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, Lauretani F, Bandinelli S, Senin U, Ferrucci L. Uric acid and inflammatory markers. Eur Heart J. 2006 May;27(10):1174-81. Epub 2006 Apr 12.
- Sitt JC, Griffith JF, Wong P. Ultrasound-guided synovial biopsy. Br J Radiol. 2016;89(1057):20150363. doi: 10.1259/bjr.20150363. Epub 2015 Nov 2. Review.
- Woollard KJ, Geissmann F. Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol. 2010 Feb;7(2):77-86. doi: 10.1038/nrcardio.2009.228. Epub 2010 Jan 12. Review.
- Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011 Oct;63(10):3136-41. doi: 10.1002/art.30520.
- 36549