L-carnitine Supplementation in Rheumatoid Arthritis Patients

Официальное название

Effect of L-carnitine Supplementation on Disease Activity in Rheumatoid Arthritis Patients

Обзор

This study aims to evaluate the effect of l-carnitine as add- on therapy for improving the outcome in rheumatoid arthritis patients.

Подробное описание

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects joints of hand, wrist and foot. Its epidemiology is more pronounced in female to male in ratio 3:1 . Etiology of the disease is related to genetics and environmental factors that lead to formation of epitopes initiating autoimmune response . It is characterized by symmetrical polyarthritis in equal or more than 5 joints and it is known that long term inflammation leads to bone deformities, cartilage damage and synovitis. signs and symptoms include pain and tenderness of joints, morning stiffness for more than 30 minutes, fever, fatigue and weight loss . Also, there are extra-articular manifestations like rheumatoid nodules , interstitial lung disease and ocular manifestations like scleritis . Many treatment approaches in RA are based on anti- inflammatory, anti-oxidant and immune suppressive drugs mainly DMARDs. Up till now, there is no anti-inflammatory agent that is both safe and effective equivalent to DMARDs which are first line of treatment and that can be a scientific gap that should be filled in future research prespectives.

L-Carnitine is a nutritional supplement that is used for enhancing performance in

exercises, valproic acid toxicity, Rett syndrome and in case of secondary carnitine deficiency like in end stage renal disease (ESRD). Physiologically, it is synthesized from lysine and methionine. It is involved in energy production by assisting in transportation of long chain fatty acid into the mitochondria where they undergo beta oxidation for ATP production. Several studies have successfully proven that it has antioxidant effect by activating PPAR gamma which is transcription factor that directly increases expression of antioxidant enzymes like super oxide dismutase (SOD) . LC also have anti-inflammatory effect by acting on PPAR gamma that also inhibits Nf-KB pathway, thus decreasing release of inflammatory mediators. That was mentioned in literature done on inflammatory diseases like coronary artery disease and sepsis . The need for an add on therapy in RA increases to improve response to treatment and provide cost effectiveness benefit that opens the door for repurposing trials.

Вмешательства

• Препарат Carnitine
  It is a nutritional supplement with trade name " Carnitol®" in Egypt.
• Препарат Disease-modifying anti-rheumatic drugs
  They are immunosuppressive drugs used to improve disease activity in Rheumatoid Arthritis patients . Conventional DMARDs include methotrexate (Imutrexate®) , leflunomide(Arthfree®) , hydroxychloroquine (plaquenil®) and sulfasalazine(colosalazine®) .

Первичные конечные точки

• change in DAS28 ESR for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]

Вторичные конечные точки (6)

• proportion of patients achieving ACR50% in both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]
• change in HAQ DI for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]
• change in TNF aplha for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]
• change in MDA for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]
• change in TAC for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]
• safety data for both arms [Срок оценки: From enrollment to the end of trial at 12 weeks]

Критерии участия

Критерии включения

• age between 18-60 years old
• diagnosed of rheumatoid arthritis according to 2010 American College of Rheumatology/European League Against Rheumatism criteria for at least 6 months
• enrolled patients treated with one of more of conventional DMARDs for ≥ 6 months with stable dose for ≥ 1 month before start of the study
• active RA despite conventional DMARDs treatment (DAS28 ESR more than or equal 3.2)
• patient or legal representative should sign informed consent

Критерии исключения

• pregnant or lactating female
• patients with liver dysfunction (>1.5x the upper limit of normal value for ALT \& AST)
• Patients with kidney dysfunction (serum creatinine more than 1.2 mg/dl)
• Patients with any active infection or concurrent malignancy
• patients with uncontrolled medical conditions or other rheumatic diseases
• patients currently taking drugs that could interact with carnitine like: warfarin

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Demerdash hospital — Cairo

Публикации

• Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980 Feb;23(2):137-45. doi: 10.1002/art.1780230202. PMID 7362664
• Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, PMID 31969328
• Yamanaka H, Tanaka E, Nakajima A, Furuya T, Ikari K, Taniguchi A, Inoue E, Harigai M. A large observational cohort study of rheumatoid arthritis, IORRA: Providing context for today's treatment options. Mod Rheumatol. 2020 Jan;30(1):1-6. doi: 10.1080/14397595.2019.1660028. Epub 2019 Oct 1. PMID 31475852
• Jiang F, Zhang Z, Zhang Y, Wu J, Yu L, Liu S. L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARgamma signaling. Mol Med Rep. 2016 Feb;13(2):1320-8. doi: 10.3892/mmr.2015.4639. Epub 2015 Dec 4. PMID 26647854
• Kiziltunc A, Cogalgil S, Cerrahoglu L. Carnitine and antioxidants levels in patients with rheumatoid arthritis. Scand J Rheumatol. 1998;27(6):441-5. doi: 10.1080/030097498442271. PMID 9855215
• Conforti A, Di Cola I, Pavlych V, Ruscitti P, Berardicurti O, Ursini F, Giacomelli R, Cipriani P. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmun Rev. 2021 Feb;20(2):102735. doi: 10.1016/j.autrev.2020.102735. Epub 2020 Dec 17. PMID 33346115
• Bongartz T, Nannini C, Medina-Velasquez YF, Achenbach SJ, Crowson CS, Ryu JH, Vassallo R, Gabriel SE, Matteson EL. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2010 Jun;62(6):1583-91. doi: 10.1002/art.27405. PMID 20155830
• Sayah A, English JC 3rd. Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol. 2005 Aug;53(2):191-209; quiz 210-2. doi: 10.1016/j.jaad.2004.07.023. PMID 16021111

Идентификаторы

NCT: NCT06753565 · RACAR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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