Antifolate Effectiveness in Arthritis

NCT00000395 | Completed Phase 2

• 2 other identifiers: R29AR042674NIAMS-035
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study looks at how the arthritis drug methotrexate works in low doses to treat rheumatoid arthritis. (High doses of methotrexate are used to treat some types of cancer.) Methotrexate blocks the action of the B-vitamin known as folic acid. We are studying the biochemical reactions affected by this vitamin because we think that blocking many of these reactions may be necessary for methotrexate to work in treating rheumatoid arthritis. Through these studies, we hope to gain a better understanding of how this drug and related drugs work as treatments for arthritis.

Conditions

Rheumatoid Arthritis; Adjuvant Arthritis

Keywords

Rheumatoid arthritis; Lewis rat adjuvant arthritis; Antifolate efficacy; Autoimmunity; Adenosine metabolism; Methotrexate therapy; Skeletal disorder; Dietary supplement; Antiarthritic agent; Folic acid

Outcome Measures

Primary Outcomes (1)

• Determine the effect of Folic acid and Folinic acid on urinary 5-amino=imidazole-4-carboxaminde (AICA in individuals with rheumatoid arthritis treated with low dose methotrexate.

Secondary Outcomes (2)

• Determine the effect of folic acid and folinic acid on urinary adenosine excretion in individuals with rheumatoid arthritis treated with low dose methotrexate

• Correlate disease activity with urinary AICA and adenosine levels

Study Arms (2)

Group 1 - Folinic acid

EXPERIMENTAL

Subjects receiving Methotrexate for 6 weeks and 5 mg of Folinic acid daily for 1 week.

Drug: Methotrexate; Dietary Supplement: Folinic acid

Group 2: Folic acid

EXPERIMENTAL

Subjects receiving Methotrexate for 6 weeks and 5 mg of Folic acid daily for 1 week.

Drug: Methotrexate; Dietary Supplement: Folic acid

Interventions

Methotrexate DRUG

Group 1 - Folinic acid; Group 2: Folic acid

Folinic acid DIETARY_SUPPLEMENT

Group 1 - Folinic acid

Folic acid DIETARY_SUPPLEMENT

Group 2: Folic acid

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals starting methotrexate for rheumatoid arthritis.
• Study subjects should not currently be taking folic acid-containing vitamins.

You may not qualify if:

• Cancer, renal, or liver disease.
• Previous use of methotrexate within the past 6 months or current use of folic acid-containing supplements.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Office of Dietary Supplements (ODS): collaborator

Study Sites (1)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (13)

• Morgan SL, Baggott JE, Vaughn WH, Young PK, Austin JV, Krumdieck CL, Alarcon GS. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 1990 Jan;33(1):9-18. doi: 10.1002/art.1780330102.

  PMID: 2405864 BACKGROUND

• Morgan SL, Baggott JE, Refsum H, Ueland PM. Homocysteine levels in patients with rheumatoid arthritis treated with low-dose methotrexate. Clin Pharmacol Ther. 1991 Nov;50(5 Pt 1):547-56. doi: 10.1038/clpt.1991.180.

  PMID: 1934868 BACKGROUND

• Morgan SL, Hine RJ, Vaughn WH, Brown A. Dietary intake and circulating vitamin levels of rheumatoid arthritis patients treated with methotrexate. Arthritis Care Res. 1993 Mar;6(1):4-10. doi: 10.1002/art.1790060103.

  PMID: 8443257 BACKGROUND

• Morgan SL, Baggott JE, Vaughn WH, Austin JS, Veitch TA, Lee JY, Koopman WJ, Krumdieck CL, Alarcon GS. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994 Dec 1;121(11):833-41. doi: 10.7326/0003-4819-121-11-199412010-00002.

  PMID: 7978695 BACKGROUND

• Morgan SL, Anderson AM, Hood SM, Matthews PA, Lee JY, Alarcon GS. Nutrient intake patterns, body mass index, and vitamin levels in patients with rheumatoid arthritis. Arthritis Care Res. 1997 Feb;10(1):9-17. doi: 10.1002/art.1790100103.

  PMID: 9313385 BACKGROUND

• Morgan SL, Baggott JE, Alarcon GS. Methotrexate in rheumatoid arthritis: folate supplementation should always be given. BioDrugs. 1997 Sep;8(3):164-75. doi: 10.2165/00063030-199708030-00002.

  PMID: 18020507 BACKGROUND

• Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998 Mar;25(3):441-6.

  PMID: 9517760 BACKGROUND

• Baggott JE, Morgan SL, Koopman WJ. The effect of methotrexate and 7-hydroxymethotrexate on rat adjuvant arthritis and on urinary aminoimidazole carboxamide excretion. Arthritis Rheum. 1998 Aug;41(8):1407-10. doi: 10.1002/1529-0131(199808)41:83.0.CO;2-H.

  PMID: 9704638 BACKGROUND

• Strand V, Morgan SL, Baggott JE, Alarcon GS. Folic acid supplementation and methotrexate efficacy: comment on articles by Schiff, Emery et al, and others. Arthritis Rheum. 2000 Nov;43(11):2615-6. doi: 10.1002/1529-0131(200011)43:113.0.CO;2-A. No abstract available.

  PMID: 11083294 BACKGROUND

• Alarcon GS, Morgan SL. Guidelines for folate supplementation in rheumatoid arthritis patients treated with methotrexate: comment on the guidelines for monitoring drug therapy. Arthritis Rheum. 1997 Feb;40(2):391; author reply 391-2. doi: 10.1002/art.1780400229. No abstract available.

  PMID: 9041955 BACKGROUND

• Morgan SL, Alarcon GS, Moreland L. Improved methotrexate patient information. Arthritis Rheum. 1995 Jun;38(6):874-5. doi: 10.1002/art.1780380633. No abstract available.

  PMID: 7779139 BACKGROUND

• Morgan Sl, Alarcon GS, Krumdieck CL. Folic acid supplementation during methotrexate therapy: it makes sense. J Rheumatol. 1993 Jun;20(6):929-30. No abstract available.

  PMID: 8350325 BACKGROUND

• Morgan SL, Oster RA, Lee JY, Alarcon GS, Baggott JE. The effect of folic acid and folinic acid supplements on purine metabolism in methotrexate-treated rheumatoid arthritis. Arthritis Rheum. 2004 Oct;50(10):3104-11. doi: 10.1002/art.20516.

  PMID: 15476202 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Experimental; Autoimmune Diseases

Interventions

Methotrexate; Leucovorin; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Coenzymes; Enzymes and Coenzymes

Study Officials

• Sarah L. Morgan, M.D., R.D.

  University of Alabama Department of Nutrition Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 1, 1996
• Primary Completion: August 1, 2002
• Study Completion: August 1, 2002
• Last Updated: December 16, 2016

Record last verified: 2013-06

Locations

US (1)