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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Phramongkutklao College of Medicine and Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 12, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2024

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 26, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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