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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06277635
• Other study ID #: TAPAC001
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: April 2025

Study information

• Verified date: February 2024
• Source: Phramongkutklao College of Medicine and Hospital
• Contact: Rattapol Pakchotanon, M.D.
• Phone: 66+2 354 7980
• Email: rattapolpmk[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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%

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Arthritis, Rheumatoid
• Collagen Diseases
• Psoriasis
• Psoriatic Arthritis
• Rheumatic Diseases
• Rheumatoid Arthritis

Intervention

Drug:
• Silymarin
Silymarin is randomly assigned to the participants for 12 weeks during study.
• Placebo
Placebo is randomly assigned to the participants for 12 weeks during study.

Locations

Country	Name	City	State
Thailand	Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine	Bangkok, Thailand, 10400	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Phramongkutklao College of Medicine and Hospital

Country where clinical trial is conducted

Thailand, 

Outcome

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