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

February 22, 2024 updated by: Phramongkutklao College of Medicine and Hospital

Effect of Silymarin Against Methotrexate-induced Liver Injury in Rheumatic Diseases, a Double-blind Randomized Controlled Trial

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

72

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Thailand
    • Bangkok
      • Bangkok, Thailand, 10400, Bangkok, Thailand, 10400
        • Recruiting
        • Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine
        • Contact:
        • Sub-Investigator:
          • Rattapol Pakchotanon, M.D.
        • Sub-Investigator:
          • Supasa Niyompanichakarn, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Silymarin group
Silymarin 140 mg oral tid pc + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks
Drug: Silymarin
Silymarin is randomly assigned to the participants for 12 weeks during study.
Other Names:
  • Milk Thistle
Placebo Comparator: Placebo group
Placebo + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks
Drug: Placebo
Placebo is randomly assigned to the participants for 12 weeks during study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AST or ALT > 1X ULN ( normal AST and ALT 0-50 U/L)
Time Frame: 12 weeks
elevation of AST or ALT more than 1X ULN (% participant)
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AST or ALT > 2X ULN ( normal AST and ALT 0-50 U/L) AST or ALT > 2X ULN AST or ALT > 2X ULN
Time Frame: 12 weeks
elevation of AST or ALT more than 2X ULN (% participant)
12 weeks
AST or ALT > 3X ULN ( normal AST and ALT 0-50 U/L)
Time Frame: 12 weeks
elevation of AST or ALT more than 3X ULN (% participant)
12 weeks
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
Time Frame: 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)
12 weeks
Discontinuation rate of methotrexate
Time Frame: 12 weeks
Rate of methotrexate discontinuation (%)
12 weeks
Adverse events
Time Frame: 12 weeks
Rate of any adverse events (%)
12 weeks
Change of DAS-28 ESR or CRP Score
Time Frame: 12 weeks
Change of DAS-28 ESR or CRP Score for patients with Rheumatoid arthritis and psoriatric arthritis (unit)
12 weeks
Change of BASDAI Score
Time Frame: 12 weeks
Change of BASDAI Score for AS (unit)
12 weeks
Change of ASDAS ESR or CRP Score
Time Frame: 12 weeks
Change of ASDAS ESR or CRP Score for AS (unit)
12 weeks
Change of BSA for psoriasis
Time Frame: 12 weeks
Change of BSA for psoriasis (unit)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phramongkutklao College of Medicine and Hospital

Investigators

  • Study Director: Rattapol Pakchotanon, M.D., Phramongkutklao College of Medicine and Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2024

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

February 12, 2024

First Submitted That Met QC Criteria

February 22, 2024

First Posted (Estimated)

February 26, 2024

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TAPAC001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study Protocol is to be shared with others. Full data would become available by mid 2026.

IPD Sharing Time Frame

mid 2026

IPD Sharing Access Criteria

IPD Sharing Access Criteria has not been decided.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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