Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01583959
Recruitment Status : Completed
First Posted : April 24, 2012
Last Update Posted : February 7, 2014
Information provided by (Responsible Party):
Varun Dhir, Postgraduate Institute of Medical Education and Research

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Folic Acid Drug: Placebo Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of 10 mg Versus 30 mg Per Week of Folic Acid in Combination With Methotrexate in Rheumatoid Arthritis
Study Start Date : April 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : December 2013

Arm Intervention/treatment
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)
Drug: Folic Acid
Folic acid tablets 5 mg

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)
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

Primary Outcome Measures :
  1. 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

  2. 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 Outcome Measures :
  1. 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

  2. Function [ Time Frame: 24 weeks ]
    Look at the function by Indian Health assessment questionnaire

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01583959

Layout table for location information
New OPD, #3035, Level 3, Rheumatology Clinic, Tuesday and Friday
Chandigarh, India, 160012
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Layout table for investigator information
Principal Investigator: Varun Dhir, MD, DM PGIMER, Chandigarh, India

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Varun Dhir, Assistant Professor, Internal Medicine, Postgraduate Institute of Medical Education and Research Identifier: NCT01583959    
Other Study ID Numbers: P-124
First Posted: April 24, 2012    Key Record Dates
Last Update Posted: February 7, 2014
Last Verified: February 2014
Keywords provided by Varun Dhir, Postgraduate Institute of Medical Education and Research:
rheumatoid arthritis
folic acid
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Folic Acid
Vitamin B Complex
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors