Clinical trial NCT01583959: Study of Different Doses of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis
Official title: Randomized Trial of 10 mg Versus 30 mg Per Week of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
folic acid
methotrexate
Lead sponsor: PIMERIndia
Sponsor class: UNKNOWN
First posted: 2012-04-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Introduction: Methotrexate is the sheet anchor for the treatment of rheumatoid arthritis. Folic acid supplementation is usually given at a dose of 5-30 mg per week to ameliorate adverse effects. Patients at our center are usually on the higher dose. However, it is unclear if higher doses are required, recent international recommendations suggest 5-10 mg per week only.

Objectives: To randomize rheumatoid patients being being started on Methotrexate into 2 groups- one on 5mg for 6 days a week (30mg per week) of folic acid and the other 5 mg twice a week (10 mg per week) for 24weeks. To look at difference in

1. Adverse effects due to methotrexate

   a. Minor adverse effects: By symptom chart

   a. Major adverse effects: Cytopenia (predefined) and transaminitis.
2. Disease activity using Disease activity score 28 joints (3 variable) and functional status by health assessment questionnaire
3. RBC folic acid levels Methodology: Randomised controlled trial, double blinded, placebo controlled. Sample size 50 in each group. One group of patients will receive folic acid 5 mg twice a week with placebo for 4 days and the other group will receive folic acid 5 mg 6 days a week for 24 weeks.

Patients will be administered adverse effects proforma, assessed for having cytopenias and transaminitis (pre defined) and disease activity will be calculated at every visit, ie., in the beginning at then at 8,16 and 24 weeks. In addition will look at the functional status and RBC folate levels at 0 and 24 weeks. Statistical analysis using chi-square test for proportions and t test for continuous variables.

Detailed description: THIS TRIAL WILL INCLUDE NEW RHEUMATOID ARTHRITIS PATIENTS These patients will then be randomized into two groups - one which continues to take the same folic acid dose and one which is shifted to folic acid 10 mg per week.

Eligibility criteria: Inclusion Criteria:

* Age 18-75 years
* Patients fulfilling the 1987 American College of Rheumatology Rheumatoid arthritis criteria

Exclusion Criteria:

* Hb less than 8 g per dl or TLC less than 3500 or Platelet less than 1 lac or SGOT or SGPT more than 60 U/L
* Serious concomitant medical illnesses such as cancer, liver or renal disease

Primary outcomes:
measure: Adverse effects
timeFrame: 24 weeks
measure: disease activity
timeFrame: 24 weeks
Secondary outcomes:
measure: RBC folic acid:
timeFrame: 24 weeks
measure: Function
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: New OPD, #3035, Level 3, Rheumatology Clinic, Tuesday and Friday
Study officials:
affiliation: PGIMER, Chandigarh, India
name: Varun Dhir, MD, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhir V, Sandhu A, Kaur J, Pinto B, Kumar P, Kaur P, Gupta N, Sood A, Sharma A, Sharma S. Comparison of two different folic acid doses with methotrexate--a randomized controlled trial (FOLVARI Study). Arthritis Res Ther. 2015 Jun 11;17(1):156. doi: 10.1186/s13075-015-0668-4.