Effect of Silymarin Against Methotrexate-induced Liver Injury in Rheumatic Diseases

Not Applicable

Recruiting

• Conditions: Psoriatic Arthritis; Rheumatoid Arthritis; Psoriasis
• Interventions: Drug: Placebo; Drug: Silymarin

• Registration Number: NCT06277635
• Lead Sponsor: Phramongkutklao College of Medicine and Hospital

Brief Summary

To study the effect of silymarin against methotrexate-induced liver injury in rheumatic diseases including rheumatoid arthritis, psoriatric arthritis and psoriasis

Detailed Description

- Methotrexate was indeed a common and effective treatment for rheumatoid arthritis, psoriatic arthritis and psoriasis. Methotrexate-related hepatotoxicity are common occur 1:1,100 persons. Liver abnormalities varies from asymptomatic liver enzyme elevation to fatal hepatic necrosis and liver fibrosis. Methotrexate was discontinued owing to liver dysfunction in 7.4%

Study Timeline

• Status Verified: 2024-02
• Study Start: 2024-02-01
• Study First Submitted: 2024-02-12
• Study First Submitted QC: 2024-02-22
• Last Update Submitted: 2024-02-22
• Study First Posted: 2024-02-26
• Last Update Posted: 2024-02-26
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• Aged > 20 years

• Diagnosis at least one of the following

  1. Rheumatoid arthritis according to American College of Rheumatology/ The European Alliance of Associations for Rheumatology 2010(ACR/EULAR2010) with at least one joint swelling or tenderness or
  2. Psoriatric arthritis according to CASPAR classification criteria with at least one joint swelling or tenderness, or at least one site dactylitis or enthesitis or Psoriasis by dermatologist with active skin lesion
  3. No previous treatment with methotrexate or treatment with methotrexate within 30 day before randomization
  4. No previous treatment with other conventional synthetic DMARDs other than methotrexate such as sulfasalazine, hydroxycholoquine, leflunomide
  5. No previous treatment with biologic DMARDs such as anti-TNF
  6. Can follow the treatment protocal

Exclusion Criteria

• Pregnancy or planning for pregnancy
• Breastfeeding women
• Ongoing treatment with active malignancy
• GFR < 30 ml/min/1.73m2
• Previous documented of HIV infection
• Chronic alcohol drinking ≥ 3 times/wk or drug abuse within 6 months prior to randomization
• Positive of HbsAg, anti HCV
• Previous documented of preexisting liver disease such as alcoholic liver disease, liver cirrhosis, autoimmune hepatitis
• AST or ALT > ULN ( 0-50 U/L )
• WBC < 3,000/ul or platelet < 100,000 /ul, ANC < 1,500/ul
• ILD diagnosed by rheumatologist and pulmonologist from chest X ray and HRCT
• History documented silymarin hypersensitivity or severe adverse effects diagnosed by physician or pharmacist from PMK hospital or from history drug allergy or symptoms such as rash, chest tightness, dyspnea, diarrhea and hypotension
• Cannot follow up on treatment protocal

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	Placebo + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks
Silymarin group	Silymarin	Silymarin 140 mg oral tid pc + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks

Primary Outcome Measures

Name	Time	Method
AST or ALT > 1X ULN ( normal AST and ALT 0-50 U/L)	12 weeks	elevation of AST or ALT more than 1X ULN (% participant)

Secondary Outcome Measures

Name	Time	Method
Change of BASDAI Score	12 weeks	Change of BASDAI Score for AS (unit)
AST or ALT > 2X ULN ( normal AST and ALT 0-50 U/L) AST or ALT > 2X ULN AST or ALT > 2X ULN	12 weeks	elevation of AST or ALT more than 2X ULN (% participant)
AST or ALT > 3X ULN ( normal AST and ALT 0-50 U/L)	12 weeks	elevation of AST or ALT more than 3X ULN (% participant)
Change of BSA for psoriasis	12 weeks	Change of BSA for psoriasis (unit)
Change of ASDAS ESR or CRP Score	12 weeks	Change of ASDAS ESR or CRP Score for AS (unit)
AST or ALT > 5X ULN or >3X ULN ( normal AST and ALT 0-50 U/L) with symptom of hepatitis such as Fatique, abdominal pain, nausea, vomiting or total bilirubin > 2X with jaundice	12 weeks	elevation of AST or ALT \> 5X ULN or \>3X ULN with symptom of hepatitis such as Fatique, abdominal pain, nausea, vomiting or total bilirubin \> 2X with jaundice (% participant)
Discontinuation rate of methotrexate	12 weeks	Rate of methotrexate discontinuation (%)
Adverse events	12 weeks	Rate of any adverse events (%)
Change of DAS-28 ESR or CRP Score	12 weeks	Change of DAS-28 ESR or CRP Score for patients with Rheumatoid arthritis and psoriatric arthritis (unit)

Trial Locations

Locations (1)

Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine; 🇹🇭 Bangkok, Thailand, 10400, Bangkok, Thailand