Assessing the Role of the NLRP3 Inflammasome in Intercritical Gout

Active, not recruiting

• Conditions: Gout
• Interventions: Procedure: Joint Biopsy

• Registration Number: NCT04125459
• Lead Sponsor: Attune Health Research, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-23
• Study First Submitted QC: 2019-10-10
• Study First Posted: 2019-10-14
• Study Start: 2020-01-22
• Primary Completion: 2021-03-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-05
• Last Update Posted: 2024-08-06
• Study Completion: 2024-10-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Adult patients with gout diagnosed by a Rheumatologist.
2. patients with a history of at least two gout attacks in the target joint
3. 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

1. Patients on anti-coagulation therapy.
2. Patients with an active infection.
3. Tophus present at the biopsy site.
4. Target joint with signs of acute gout attack (pain >7/10, redness, warmth)
5. Known chondrocalcinosis

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Individuals with Gout	Joint Biopsy	This arm will be getting a biopsy as well as a blood draw

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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
Microcrystal Correlation	Up to 2 months	Correlate NLRP3 activity with the presence of microcrystals in the synovium

Trial Locations

Locations (1)

Attune Health Research Inc.; 🇺🇸 Beverly Hills, California, United States