Clinical trial NCT06277635: Effect of Silymarin Against Methotrexate-induced Liver Injury in Rheumatic Diseases
Official title: Effect of Silymarin Against Methotrexate-induced Liver Injury in Rheumatic Diseases, a Double-blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rheumatoid Arthritis
Psoriatic Arthritis
Psoriasis
Keywords: Rheumatoid arthritis
Psoriatric arthritis
Psoriasis
Methotrexate
Silymarin
Lead sponsor: Phramongkutklao College of Medicine and Hospital
Sponsor class: OTHER
First posted: 2024-02-26
Enrollment: 72
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%

Eligibility criteria: 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

Primary outcomes:
measure: AST or ALT > 1X ULN ( normal AST and ALT 0-50 U/L)
timeFrame: 12 weeks
Secondary outcomes:
measure: AST or ALT > 2X ULN ( normal AST and ALT 0-50 U/L) AST or ALT > 2X ULN AST or ALT > 2X ULN
timeFrame: 12 weeks
measure: AST or ALT > 3X ULN ( normal AST and ALT 0-50 U/L)
timeFrame: 12 weeks
measure: 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
timeFrame: 12 weeks
measure: Discontinuation rate of methotrexate
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
measure: Change of DAS-28 ESR or CRP Score
timeFrame: 12 weeks
measure: Change of BASDAI Score
timeFrame: 12 weeks
measure: Change of ASDAS ESR or CRP Score
timeFrame: 12 weeks
measure: Change of BSA for psoriasis
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bangkok, Thailand, 10400
country: Thailand
facility: Rheumatic Disease Unit, Department of Internal Medicine, Phramongkutklao Hospital and College of Medicine
state: Bangkok
Study officials:
affiliation: Phramongkutklao College of Medicine and Hospital
name: Rattapol Pakchotanon, M.D.
role: STUDY_DIRECTOR
References: