A study to determine the optimal dose of folic acid supplementation in patients with rheumatic diseases on methotrexate treatment

JRCT ID: jRCT1061230085

Registered date:26/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients on methotrexate therapy regularly take folic acid supplementation to prevent its toxicity.
• Date of first enrollment: 26/12/2023
• Target sample size: 50
• Study type: Interventional
• Intervention(s): In the ARM-1 group, 24 hours after the last dose of methotrexate from Day 1 to Day 84, folamine 5 mg 2 tablets per week is administered. In the ARM-2 group, foliamine 5 mg 1 tablet per week is administered 24 hours after the last dose of methotrexate from Day 1 to Day 84.

Outcome(s)

• Primary Outcome: The incidence of liver damage 12 weeks after the start of treatment was compared betwee the ARM-1 group, in which folic acid 10 mg per week was supplemented 24 hours after the last dose of methotrexate and the ARM-2 group, in which folic acid was supplemented with 5 mg per week 24 hours after the last dose of methotrexate.

Secondary Outcome

1. The changes in liver enzymes (AST, ALT) from baseline (Day0) to 12 weeks (Day84) after the start of treatment are compared between the ARM-1 and ARM-2 groups. In addition, this comparison is evaluated after stratifying by cases with and without liver damage at baseline.
2. The clinical characteristics of patients are identified in whom folic acid supplementation of 10 mg/week is more favorable in terms of MTX-associated liver injury are determined.
3. The changes of patient reported outcomes (PRO) and blood tests (blood cells, MCV, liver enzymes, CRP, blood sedimentation) from baseline to 12 weeks after the start of treatment are compared in the ARM-1 group.
4. The proportion of patients in the ARM-1 and ARM-2 groups are compared who required additional administration or change of rheumatoid arthritis drugs, steroids or immunosuppressants because of the worsening the disease activity and drug adverse events during the observation period.
5. The relationship is investigated between the concentration of polyglutamated methotrexate in red blood cells and disease activity of RA (SDAI, CDAI), overall disease activity (CRP, ESR), methotrexate side effects (oral ulcer, gastrointestinal symptom, hematological disorder, liver damage), folic acid supplementation amount, renal function (eGFR), and BMI at Day84.
6. The differences of the concentration of polyglutamate methotrexate in red blood cells are compared between patients with rheumatoid arthritis and patients with other rheumatic diseases at Day0.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Adult patients aged 18 years or older at the time of consent
2. Patients who were diagnosed with rheumatic disease more than 12 weeks ago and have been receiving stable doses of methotrexate for more than 8 weeks
3. Patients receiving folic acid 5 mg/week 24-48 hours after the last dose of methotrexate
4. Patients whose written consent are obtained for participation in this study

Exclude criteria

1. Patients who have regularly taken supplements or health foods containing folic acid within 8 weeks before starting this study
2. Patients who are lack of medication compliance due to cognitive impairment
3. Patients who are unable to visit our hospital regularly during the 12-week study period
4. Patients judged to be inappropriate by the principal investigator or sub-investigator

Related Information

• Primary Sponsor: Shintaro Hirata
• Source(s) of Monetary Support: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital