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

This study is currently recruiting participants.
Verified January 2013 by Postgraduate Institute of Medical Education and Research
Sponsor:
Information provided by (Responsible Party):
Varun Dhir, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT01583959
First received: March 15, 2012
Last updated: January 2, 2013
Last verified: January 2013
History of Changes
  Purpose

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 Intervention Phase
Rheumatoid Arthritis
 Drug: Folic Acid
Drug: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Postgraduate Institute of Medical Education and Research:

Primary Outcome Measures:
  • Adverse effects [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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:
  • RBC folic acid: [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    This will be done by chemiluminescence assay, to compare folic acid levels at baseline and at 24 weeks

  • Function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Look at the function by Indian Health assessment questionnaire


Estimated Enrollment: 100
Study Start Date: April 2012
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01583959

Contacts
Contact: Varun Dhir, MD, DM 8872229998 varundhir@gmail.com

Locations
India
New OPD, #3035, Level 3, Rheumatology Clinic, Tuesday and Friday Recruiting
Chandigarh, India, 160012
Contact: Varun Dhir, MD, DM     8872229998     varundhir@gmail.com    
Principal Investigator: Varun Dhir, MD, DM            
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
Principal Investigator: Varun Dhir, MD, DM PGIMER, Chandigarh, India
  More Information

No publications provided

Responsible Party: Varun Dhir, Assistant Professor, Internal Medicine, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT01583959     History of Changes
Other Study ID Numbers: P-124
Study First Received: March 15, 2012
Last Updated: January 2, 2013
Health Authority: India: IEC

Keywords provided by Postgraduate Institute of Medical Education and Research:
rheumatoid arthritis
folic acid
methotrexate

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Folic Acid Antagonists
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Hematinics
Methotrexate
Vitamins
Micronutrients
 Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematologic Agents
Therapeutic Uses
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 18, 2013