Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, Psoriatric arthritis, Psoriasis, Methotrexate, Silymarin
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%
Interventions
DRUGSilymarin
Silymarin is randomly assigned to the participants for 12 weeks during study.
DRUGPlacebo
Placebo is randomly assigned to the participants for 12 weeks during study.
Sponsors
Phramongkutklao College of Medicine and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AST or ALT > 1X ULN ( normal AST and ALT 0-50 U/L) | 12 weeks | elevation of AST or ALT more than 1X ULN (% participant) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | elevation of AST or ALT more than 2X ULN (% participant) |
| 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 | 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) |
| Discontinuation rate of methotrexate | 12 weeks | Rate of methotrexate discontinuation (%) |
| Adverse events | 12 weeks | Rate of any adverse events (%) |
| AST or ALT > 3X ULN ( normal AST and ALT 0-50 U/L) | 12 weeks | elevation of AST or ALT more than 3X ULN (% participant) |
| Change of BASDAI Score | 12 weeks | Change of BASDAI Score for AS (unit) |
| Change of ASDAS ESR or CRP Score | 12 weeks | Change of ASDAS ESR or CRP Score for AS (unit) |
| Change of BSA for psoriasis | 12 weeks | Change of BSA for psoriasis (unit) |
| Change of DAS-28 ESR or CRP Score | 12 weeks | Change of DAS-28 ESR or CRP Score for patients with Rheumatoid arthritis and psoriatric arthritis (unit) |
Countries
Thailand
Contacts
Primary ContactRattapol Pakchotanon, M.D.
Backup ContactChatpong Makmee, M.D.
Outcome results
None listed