The Effect of Cilostazol on Rheumatoid Arthritis Patients

Summary

The goal of this study is to evaluate the effect of cilostazol on Rheumatoid Arthritis patients. It aims to answer the questions of : 1. Will Cilostazol improve the disease severity and quality of life in Rheumatoid arthritis patients? 2. Will Cilostazol decrease the oxidative stress, inflammation and endothelial dysfunction in Rheumatoid arthritis patients? Participants will be randomized into two arms either treatment or control the treatment group will be asked to take Cilostazol 100 mg twice daily in addition to the usual DMARD (Methotrexate , Sulfasalazine , Hydroxychloroquine or Leflunomide), while the control group will be taking the usual DMARDs only. Patients in both arms will be followed-up every 2 weeks through out the 6-month duration of the study.

Timeline

Start

2022-11-01

Primary completion

2024-10-01

Completion

2024-10-01

Publications

• Background Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol Int. 2021 May;41(5):863-877. doi: 10.1007/s00296-020-04731-0. Epub 2020 Nov 11.
• Background Castrejon I, Ortiz AM, Toledano E, Castaneda S, Garcia-Vadillo A, Patino E, Gonzalez-Alvaro I. Estimated cutoff points for the 28-joint disease activity score based on C-reactive protein in a longitudinal register of early arthritis. J Rheumatol. 2010 Jul;37(7):1439-43. doi: 10.3899/jrheum.091333. Epub 2010 May 15.
• Background Cha Y, Erez T, Reynolds IJ, Kumar D, Ross J, Koytiger G, Kusko R, Zeskind B, Risso S, Kagan E, Papapetropoulos S, Grossman I, Laifenfeld D. Drug repurposing from the perspective of pharmaceutical companies. Br J Pharmacol. 2018 Jan;175(2):168-180. doi: 10.1111/bph.13798. Epub 2017 May 18.
• Background Conigliaro P, Triggianese P, De Martino E, Fonti GL, Chimenti MS, Sunzini F, Viola A, Canofari C, Perricone R. Challenges in the treatment of Rheumatoid Arthritis. Autoimmun Rev. 2019 Jul;18(7):706-713. doi: 10.1016/j.autrev.2019.05.007. Epub 2019 May 3.
• Background da Motta NA, de Brito FC. Cilostazol exerts antiplatelet and anti-inflammatory effects through AMPK activation and NF-kB inhibition on hypercholesterolemic rats. Fundam Clin Pharmacol. 2016 Aug;30(4):327-37. doi: 10.1111/fcp.12195. Epub 2016 Mar 31.
• Background Das DC, Jahan I, Uddin MG, Hossain MM, Chowdhury MAZ, Fardous Z, Rahman MM, Kabir AKMH, Deb SR, Siddique MAB, Das A. Serum CRP, MDA, Vitamin C, and Trace Elements in Bangladeshi Patients with Rheumatoid Arthritis. Biol Trace Elem Res. 2021 Jan;199(1):76-84. doi: 10.1007/s12011-020-02142-7. Epub 2020 Apr 18.
• Background Ferro F, Elefante E, Luciano N, Talarico R, Todoerti M. One year in review 2017: novelties in the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2017 Sep-Oct;35(5):721-734. Epub 2017 Sep 13.
• Background Foster W, Carruthers D, Lip GY, Blann AD. Inflammatory cytokines, endothelial markers and adhesion molecules in rheumatoid arthritis: effect of intensive anti-inflammatory treatment. J Thromb Thrombolysis. 2010 May;29(4):437-42. doi: 10.1007/s11239-009-0370-y.
• Background 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.
• Background Gaffo A, Saag KG, Curtis JR. Treatment of rheumatoid arthritis. Am J Health Syst Pharm. 2006 Dec 15;63(24):2451-65. doi: 10.2146/ajhp050514.
• Background Garcia-Gonzalez A, Gaxiola-Robles R, Zenteno-Savin T. Oxidative stress in patients with rheumatoid arthritis. Rev Invest Clin. 2015 Jan-Feb;67(1):46-53.
• Background Kim HY, Lee SW, Park SY, Baek SH, Lee CW, Hong KW, Kim CD. Efficacy of concurrent administration of cilostazol and methotrexate in rheumatoid arthritis: pharmacologic and clinical significance. Life Sci. 2012 Sep 17;91(7-8):250-7. doi: 10.1016/j.lfs.2012.07.003. Epub 2012 Jul 20.
• Background Lee YS, Lee SY, Park SY, Lee SW, Hong KW, Kim CD. Cilostazol add-on therapy for celecoxib synergistically inhibits proinflammatory cytokines by activating IL-10 and SOCS3 in the synovial fibroblasts of patients with rheumatoid arthritis. Inflammopharmacology. 2019 Dec;27(6):1205-1216. doi: 10.1007/s10787-019-00605-5. Epub 2019 May 23.
• Background Lin YJ, Anzaghe M, Schulke S. Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells. 2020 Apr 3;9(4):880. doi: 10.3390/cells9040880.
• Background Liu T, Zhang L, Joo D, Sun SC. NF-kappaB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023-. doi: 10.1038/sigtrans.2017.23. Epub 2017 Jul 14.
• Background Matcham F, Scott IC, Rayner L, Hotopf M, Kingsley GH, Norton S, Scott DL, Steer S. The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014 Oct;44(2):123-30. doi: 10.1016/j.semarthrit.2014.05.001. Epub 2014 May 29.
• Background El Meidany YM, El Gaafary MM, Ahmed I. Cross-cultural adaptation and validation of an Arabic Health Assessment Questionnaire for use in rheumatoid arthritis patients. Joint Bone Spine. 2003 Jun;70(3):195-202. doi: 10.1016/s1297-319x(03)00004-6.
• Background Noack M, Miossec P. Selected cytokine pathways in rheumatoid arthritis. Semin Immunopathol. 2017 Jun;39(4):365-383. doi: 10.1007/s00281-017-0619-z. Epub 2017 Feb 17.
• Background Picerno V, Ferro F, Adinolfi A, Valentini E, Tani C, Alunno A. One year in review: the pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2015 Jul-Aug;33(4):551-8. Epub 2015 Jul 21.
• Background Pisetsky DS. Advances in the Treatment of Rheumatoid Arthritis: Costs and Challenges. N C Med J. 2017 Sep-Oct;78(5):337-340. doi: 10.18043/ncm.78.5.337.
• Background Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A, Sanseau P, Cavalla D, Pirmohamed M. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019 Jan;18(1):41-58. doi: 10.1038/nrd.2018.168. Epub 2018 Oct 12.
• Background Refaie MMM, Ahmed Ibrahim R, Shehata S. Dose dependent effect of cilostazol in induced testicular ischemia reperfusion via modulation of HIF/VEGF and cAMP/SIRT1 pathways. Int Immunopharmacol. 2021 Dec;101(Pt A):108197. doi: 10.1016/j.intimp.2021.108197. Epub 2021 Oct 6.
• Background Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl). 2011 Jul;89(7):667-76. doi: 10.1007/s00109-011-0748-0. Epub 2011 Mar 23.
• Background Samimi Z, Kardideh B, Zafari P, Bahrehmand F, Roghani SA, Taghadosi M. The impaired gene expression of adenosine monophosphate-activated kinase (AMPK), a key metabolic enzyme in leukocytes of newly diagnosed rheumatoid arthritis patients. Mol Biol Rep. 2019 Dec;46(6):6353-6360. doi: 10.1007/s11033-019-05078-x. Epub 2019 Nov 18.
• Background Sarban S, Kocyigit A, Yazar M, Isikan UE. Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. Clin Biochem. 2005 Nov;38(11):981-6. doi: 10.1016/j.clinbiochem.2005.08.003. Epub 2005 Sep 16.
• Background Sorkin EM, Markham A. Cilostazol. Drugs Aging. 1999 Jan;14(1):63-71; discussion 72-3. doi: 10.2165/00002512-199914010-00005.
• Background Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019 Jan 1;170(1):ITC1-ITC16. doi: 10.7326/AITC201901010.
• Background Suzuki K, Uchida K, Nakanishi N, Hattori Y. Cilostazol activates AMP-activated protein kinase and restores endothelial function in diabetes. Am J Hypertens. 2008 Apr;21(4):451-7. doi: 10.1038/ajh.2008.6. Epub 2008 Feb 7.
• Background Usenbo A, Kramer V, Young T, Musekiwa A. Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis. PLoS One. 2015 Aug 4;10(8):e0133858. doi: 10.1371/journal.pone.0133858. eCollection 2015.
• Background van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-K.
• Background Charles J, Britt H, Pan Y. Rheumatoid arthritis. Aust Fam Physician. 2013 Nov;42(11):765.
• Background Yoshida Y, Tanaka T. Interleukin 6 and rheumatoid arthritis. Biomed Res Int. 2014;2014:698313. doi: 10.1155/2014/698313. Epub 2014 Jan 12.

Drugs

Indications