Immune Molecular and Inflammatory Cytokines Dysfunction Analysis in Gout Patients With Different Urate Levels

Study Overview
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Brief Summary
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The aim of study was to assess the efficiency and safety of oral IL-1βinhibitor in combination with urate lowering therapy on joint pain intensity,urate control, global assessments of disease activity, self-monitored gouty acute flare times, inflammatory markers and symptoms improving related life quantity in gouty patients.

Detailed Description
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This was a randomized single-dose, open-label and active-controlled study which was carried out in 96 primary gout patients. Subjects and doctors have no access to randomization sequence which is determined by the primary investigator.All patients received an open-label febuxostat 40mg daily during the whole study. Healthy control were 32 age-matched men from volunteers in the medical health center.Two primary end points included pain intensity measurement which was recorded at each visit and subsequently acute flare times which was recorded at home and reported to investigator.

Official Title
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Diacerein Combined With Febuxostat Relieves Symptoms of Gout by Suppressing IL-1βinflammation

Conditions
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Primary Gout

Intervention / Treatment
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* Drug: Diacerein
* Drug: Colchicine
* Drug: Febuxostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants who were allocated to the study all had a history of taking tolerable and adequate dose of urate lowering therapy including febuxostat 40-80mg daily or allopurinol 200-300 mg daily for at least 4 weeks and were defined as difficult to treat or refractory gout patients. All patients had a negative of rheumatoid factor and antinuclear antibody, Hb>100g/L, total leukocyte count≥3.5×109, PLT≥80×109, serum creatinine<133umol/L, transaminases<60U/L and fasting urate≥6.0mg/dL. Inclusion criteria for the gouty patients were age≥18 years old, BMI(18-30kg/m2). All participants enrolled in our study fulfilled American College of Rheumatology criteria for primary gout. Exclusion Criteria: Exclusion criteria included secondary gout (because it is always associated with some underlying renal disease), a history of congestive heart failure, serum creatinine≥133umol/L (because the patients have underlying risks if NSAID needed) or the use of glucocorticoid>15mg daily,colchicine, uricosuric drugs, chemotherapy or immunosuppressive therapy in the past three months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Febuxostat<br>Febuxostat 40mg once a day | Drug: Febuxostat<br>* A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout<br>* Other names: No other names;|
| Experimental: Febuxostat plus diacerein<br>Febuxostat 40mg once a day plus diacerein 50mg twice a day | Drug: Diacerein<br>* oral administration of IL-1βinhibitory<br>* Other names: Diacetylrhein;Drug: Febuxostat<br>* A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout<br>* Other names: No other names;|
| Experimental: Febuxostat plus Colchicine<br>Febuxostat 40mg once a day plus Colchicine 0.5mg twice a day | Drug: Colchicine<br>* Colchicine is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum (autumn crocus, Colchicum autumnale, also known as meadow saffron). It was used originally to treat rheumatic complaints, especially gout as the positive control<br>* Other names: Generics;Drug: Febuxostat<br>* A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout<br>* Other names: No other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients'intensity of pain | Patients' intensity of pain was assessed at each visit by a single question using a 100mm visual analogue scale (VAS). The pain question was how much pains have you had because of your illness in the past seven days? The two anchors were no pain (0 score) and unbearable pain (score of 100). Patients were instructed to draw a vertical mark on the scaleline and the investigator measured the length and recorded the result. | 12 weeks | 
| Acute gout flare times | Acute gout flare was defined by pain, redness, swelling, and warmth on joints or adjacent soft tissue and pain VAS more than 3.0. For subsequent gout flares, subjects were recorded events by themselves and were reported to investigator whether they had any new or recurrent gout flares since their last visit | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum and urine urate concentration | serum urate concentration and 24h urine urate concentration | 24 weeks | 
| HAQ | Healthy Assessment Questionnaire (HAQ) disability index might be valuable to assess the joints function impaired by gout flares.HAQ comprised twenty questions and each question has a corresponding mark : 0, 1 or 2. Sum of each answer of the questions was divided by 20 | 12 weeks | 
| Flow Cytometry analysis on cell markers | Inhibitory T cell:CD4 Help T cell:CD8 Natural Killer cell:CD56,CD69，CD16 and CD25 (CD 56 dim and CD56 bright) B cell:CD19 and CD20 | 12 weeks | 
| Quantitative PCR for mRNA expression of inflammatory cytokines on PBMC | IL-1β,IL-18, IL-10 | 12 weeks | 
| Serum concentration of inflammatory cytokines | IL-1β，IL-10，IL-6 and IL-8 etc. | 12 weeks |