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

NCT06277635 | Recruiting

• 1 other identifier: TAPAC001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rheumatoid Arthritis; Psoriatic Arthritis; Psoriasis

Keywords

Rheumatoid arthritis; Psoriatric arthritis; Psoriasis; Methotrexate; Silymarin

Outcome Measures

Primary Outcomes (1)

• AST or ALT > 1X ULN ( normal AST and ALT 0-50 U/L)

  elevation of AST or ALT more than 1X ULN (% participant)

  12 weeks

Secondary Outcomes (9)

• 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

• AST or ALT > 3X ULN ( normal AST and ALT 0-50 U/L)

  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

  12 weeks

• Discontinuation rate of methotrexate

  12 weeks

• Adverse events

  12 weeks

Study Arms (2)

Silymarin group

ACTIVE COMPARATOR

Silymarin 140 mg oral tid pc + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks

Drug: Silymarin

Placebo group

PLACEBO COMPARATOR

Placebo + methotrexate weekly + folic acid 5 mg oral OD pc for 12 weeks

Drug: Placebo

Interventions

Silymarin DRUG

Silymarin is randomly assigned to the participants for 12 weeks during study.

Also known as: Milk Thistle

Silymarin group

Placebo DRUG

Placebo is randomly assigned to the participants for 12 weeks during study.

Placebo group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \> 20 years
• Diagnosis at least one of the following
• 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
• 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
• No previous treatment with methotrexate or treatment with methotrexate within 30 day before randomization
• No previous treatment with other conventional synthetic DMARDs other than methotrexate such as sulfasalazine, hydroxycholoquine, leflunomide
• No previous treatment with biologic DMARDs such as anti-TNF
• Can follow the treatment protocal

You may not qualify if:

• 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

Sponsors & Collaborators

• Phramongkutklao College of Medicine and Hospital: lead

Study Sites (1)

Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine

Bangkok, Thailand, 10400, Bangkok, 10400, Thailand

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Psoriatic; Psoriasis

Interventions

Silymarin; milk-thistle extract

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Skin Diseases, Papulosquamous; Skin Diseases

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Rattapol Pakchotanon, M.D.

  Phramongkutklao College of Medicine and Hospital

  STUDY DIRECTOR

Central Study Contacts

Rattapol Pakchotanon, M.D.

CONTACT

66+2 354 7980; rattapolpmk@gmail.com

Chatpong Makmee, M.D.

CONTACT

0862204693; chatpongmakmee17@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 26, 2024
• Study Start: February 1, 2024
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: mid 2026
• Access Criteria: IPD Sharing Access Criteria has not been decided.

Locations

TH (1)