Study of Different Doses of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis

Overview

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.

Full Title of Study: “Randomized Trial of 10 mg Versus 30 mg Per Week of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2013

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.

Interventions

  • Drug: Folic Acid
    • Folic acid tablets 5 mg
  • Drug: Placebo
    • Matched placebo to folic acid 5 mg tables, to be given for 4 days a week

Arms, Groups and Cohorts

  • Active Comparator: Folic acid 30 mg per week
    • Patients will be administered 5 mg folic acid for 6 days a week, no tablet on the day they take methotrexate (5 mg x 6 days = 30 mg per week)
  • Active Comparator: Folic acid 10 mg
    • Patients will be given folic acid 5 mg for two days per week and placebo tablets for four days a week, no tablet on the day they take methotrexate (Folic acid 5mg x 2 days = 10mg per week)

Clinical Trial Outcome Measures

Primary Measures

  • Adverse effects
    • Time Frame: 24 weeks
    • i. Minor: Two Symptom charts: Those AEs related temporally to methotrexate and those not temporally related. ii. Major: Hemoglobin (Hb), Platelet, Total leucocyte count or white blood count (TLC), Differential leukocyte count (DLC), Serum glutamic oxaloacetate transaminase (SGOT)/ serum glutamic pyruvate transaminase (SGPT) will be done at 3 months. Patients having Hb≤6, TLC ≤ 3500, Platelet ≤99000, SGOT or SGPT ≥80 IU/L
  • disease activity
    • Time Frame: 24 weeks
    • Using disease activity score 28 joints 3 variables(DAS 28-3v) : uses evaluation of tender joint count (TJC28), Swollen joint count (SJC28) and the erythrocyte sedimentation rate (ESR) using Westergren method.

Secondary Measures

  • RBC folic acid:
    • Time Frame: 24 weeks
    • This will be done by chemiluminescence assay, to compare folic acid levels at baseline and at 24 weeks
  • Function
    • Time Frame: 24 weeks
    • Look at the function by Indian Health assessment questionnaire

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Post Graduate Institute of Medical Education and Research, Chandigarh
  • Provider of Information About this Clinical Study
    • Principal Investigator: Varun Dhir, Assistant Professor, Internal Medicine – Post Graduate Institute of Medical Education and Research, Chandigarh
  • Overall Official(s)
    • Varun Dhir, MD, DM, Principal Investigator, PGIMER, Chandigarh, India

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.