Teriflunomide's Therapeutic Mechanisms of Action in Patients With Relapsing Remitting Multiple Sclerosis.
14. september 2017 opdateret af: University of North Carolina, Chapel Hill
Characterization of Teriflunomide's Therapeutic Mechanisms of Action in Patients With Relapsing Remitting Multiple Sclerosis.
The purpose of this research is to characterize the effect of teriflunomide on the activation of B-cells, as well as its capacity to modify B-cell cytokine secretion.
The in-vitro identified effects of teriflunomide on the expression of B-cell activation markers, costimulatory and antigen presenting molecules, as well as on cytokine secretion, will then be confirmed in a cohort of Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with this medication.
Studieoversigt
Status
Afsluttet
Betingelser
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
26
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- University of North Carolina
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 55 år (Voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
Neurology/MS clinic: patients with Relapsing Remitting MS "Treatment naïve Relapsing Remitting MS patients will be recruited to provide samples for the in vitro tests.
In addition, Relapsing Remitting MS patients who are already receiving treatment with teriflunomide as a part of their routine care will be recruited to obtain blood samples for the in vivo testing."
Beskrivelse
Inclusion Criteria:
- confirmed diagnosis of RRMS according to McDonald's diagnostic criteria,
- age 18-55,
- an extended disability status score (EDSS) of 1.5-5.5.
Exclusion Criteria:
- Previous treatment with DMT.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
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Percent Inhibition of activated/memory B-cells derived from RRMS patients.
Tidsramme: 1 year
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1 year
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Change in Cytokine Secretion Profile of T-cells stimulated by teriflunomide treatment
Tidsramme: 1 year
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1 year
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Measure the effect of oral teriflunomide on the cytokine secretion as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Tidsramme: 1 year
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1 year
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Measure the effect of oral teriflunomide on the B cell activation as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Tidsramme: 1 year
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1 year
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Silva MarkovicPlese, MD, Universtiy of North Carolina at Chapel Hill
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6;365(14):1293-303. doi: 10.1056/NEJMoa1014656.
- Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.
- Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.
- Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6.
- Li L, Liu J, Delohery T, Zhang D, Arendt C, Jones C. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J Neuroimmunol. 2013 Dec 15;265(1-2):82-90. doi: 10.1016/j.jneuroim.2013.10.003. Epub 2013 Oct 12.
- Claussen MC, Korn T. Immune mechanisms of new therapeutic strategies in MS: teriflunomide. Clin Immunol. 2012 Jan;142(1):49-56. doi: 10.1016/j.clim.2011.02.011. Epub 2011 Mar 1.
- Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol. 1999 Feb 15;162(4):2095-102.
- Prineas JW, Wright RG. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest. 1978 Apr;38(4):409-21.
- Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, Calabresi PA, Waubant E, Hauser SL, Zhang J, Smith CH. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol. 2010 Apr;67(4):452-61. doi: 10.1002/ana.21939.
- Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.
- Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998 Oct 15;161(8):3912-8.
- Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol. 2006 Oct 1;177(7):4481-7. doi: 10.4049/jimmunol.177.7.4481.
- Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL. Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells. Eur J Immunol. 2007 Sep;37(9):2400-4. doi: 10.1002/eji.200737296.
- Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y. Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.
- Ramgolam VS, Sha Y, Marcus KL, Choudhary N, Troiani L, Chopra M, Markovic-Plese S. B cells as a therapeutic target for IFN-beta in relapsing-remitting multiple sclerosis. J Immunol. 2011 Apr 1;186(7):4518-26. doi: 10.4049/jimmunol.1000271. Epub 2011 Mar 2.
- Zhang X, Tao Y, Troiani L, Markovic-Plese S. Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell differentiation in CD4+ T cells derived from patients with multiple sclerosis. J Immunol. 2011 Sep 15;187(6):3431-7. doi: 10.4049/jimmunol.1100580. Epub 2011 Aug 19.
- Dimitrova P, Skapenko A, Herrmann ML, Schleyerbach R, Kalden JR, Schulze-Koops H. Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiation. J Immunol. 2002 Sep 15;169(6):3392-9. doi: 10.4049/jimmunol.169.6.3392.
- Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002 Oct;3(10):944-50. doi: 10.1038/ni833. Epub 2002 Sep 3.
- Zhang X, Tao Y, Chopra M, Ahn M, Marcus KL, Choudhary N, Zhu H, Markovic-Plese S. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013 Dec 15;191(12):5867-74. doi: 10.4049/jimmunol.1301926. Epub 2013 Nov 6.
- Hirotani M, Niino M, Fukazawa T, Kikuchi S, Yabe I, Hamada S, Tajima Y, Sasaki H. Decreased IL-10 production mediated by Toll-like receptor 9 in B cells in multiple sclerosis. J Neuroimmunol. 2010 Apr 15;221(1-2):95-100. doi: 10.1016/j.jneuroim.2010.02.012. Epub 2010 Mar 15.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. januar 2016
Primær færdiggørelse (Faktiske)
21. december 2016
Studieafslutning (Faktiske)
21. december 2016
Datoer for studieregistrering
Først indsendt
21. juni 2016
Først indsendt, der opfyldte QC-kriterier
12. juli 2016
Først opslået (Skøn)
14. juli 2016
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
15. september 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
14. september 2017
Sidst verificeret
1. september 2017
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 14-2877
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
UBESLUTET
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