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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Gout
• Intervention / Treatment: Drug: Febuxostat; Drug: Diacerein; Drug: Colchicine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Yikai YU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Febuxostat; Febuxostat 40mg once a day	Drug: Febuxostat; A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout; Other Names: No other names
Experimental: Febuxostat plus diacerein; Febuxostat 40mg once a day plus diacerein 50mg twice a day	Drug: Febuxostat; A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout; Other Names: No other names; Drug: Diacerein; oral administration of IL-1βinhibitory; Other Names: Diacetylrhein
Experimental: Febuxostat plus Colchicine; Febuxostat 40mg once a day plus Colchicine 0.5mg twice a day	Drug: Febuxostat; A urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and gout; Other Names: No other names; Drug: Colchicine; 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; Other Names: Colcrys; Generics

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Shaoxian HU, Doctor, Tongji Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 8, 2014
• First Submitted That Met QC Criteria: February 8, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Estimate): May 8, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine; Febuxostat; Diacetylrhein
• Other Study ID Numbers: Diagout1