Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
40 participants
INTERVENTIONAL
1996-09-30
2002-08-31
Brief Summary
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Detailed Description
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Several studies indicate that supplemental folinic acid (5-formyltetrahydrofolate) used in large doses during low-dose methotrexate therapy for rheumatoid arthritis causes a flare in joint inflammation. However, supplemental folic acid (pteroylglutamic acid) does not lessen the efficacy of the therapy. We further hypothesize that if methotrexate efficacy is driven by aminoimidazole carboxamide ribotide transformylase inhibition, folic acid supplementation should not alter urinary levels of aminoimidazole carboxamide, adenosine, and deoxyadenosine, while folinic acid supplementation should prevent the accumulation of these compounds.
We will test our hypotheses both in people with rheumatoid arthritis and in Lewis rat adjuvant arthritis. Our objectives include: (1) determining if the dose level of methotrexate that is clinically optimal in the treatment of Lewis rat adjuvant arthritis interferes with normal adenosine metabolism; (2) determining the effectiveness of drugs that interfere with adenosine metabolism (deoxycoformycin, aminoimidazole carboxamide, and aminoimidazole carboxamide with a suboptimal dose of methotrexate) in Lewis rat adjuvant arthritis; and (3) determining whether supplemental folic acid and folinic acid during methotrexate therapy normalize adenosine metabolism in patients with rheumatoid arthritis. The information we obtain will enhance the understanding of the biochemical action of antifolates/antimetabolites that are effective in the treatment of human and animal arthritis.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
DIAGNOSTIC
DOUBLE
Study Groups
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Group 1 - Folinic acid
Subjects receiving Methotrexate for 6 weeks and 5 mg of Folinic acid daily for 1 week.
Methotrexate
Folinic acid
Group 2: Folic acid
Subjects receiving Methotrexate for 6 weeks and 5 mg of Folic acid daily for 1 week.
Methotrexate
Folic acid
Interventions
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Methotrexate
Folinic acid
Folic acid
Eligibility Criteria
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Inclusion Criteria
* Study subjects should not currently be taking folic acid-containing vitamins.
Exclusion Criteria
* Previous use of methotrexate within the past 6 months or current use of folic acid-containing supplements.
18 Years
85 Years
ALL
No
Sponsors
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
NIH
Office of Dietary Supplements (ODS)
NIH
University of Alabama at Birmingham
OTHER
Responsible Party
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Principal Investigators
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Sarah L. Morgan, M.D., R.D.
Role: PRINCIPAL_INVESTIGATOR
University of Alabama Department of Nutrition Sciences
Locations
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The University of Alabama at Birmingham
Birmingham, Alabama, United States
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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