- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00561548
Impact of Anti-Tumor Necrosis Factor (TNF) Antibodies on the T-lymphocyte and Macrophage Cooperation in Crohn Disease
Impact of Anti-TNF Antibodies on the T-lymphocyte and Macrophage Cooperation in the Crohn Disease
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Crohn disease is an inflammatory disease and its frequency has been increasing over the last 25 years. The physiopathology involves a failure in the negative regulatory mechanisms of the inflammatory responses in the intestines, along with an excessive production of TNF-α by T-lymphocytes and macrophages of the lamina propria.
Anti-TNF-α antibodies usually give good therapeutic results, in particular in patients who are resistent or dependant on steroids. Nevertheless, in Crohn disease, the destructive T-lymphocytes - macrophage interactions, their inhibition by anti-TNFα, and the impact of these antibodies on cellular signaling remain largely unknown.
Two groups of 10 patients with active Crohn disease, with or without azathioprine, and requiring the start of anti-TNF treatment are included in this study. Rectosigmoïdal biopsies and blood tests will be done before starting the treatment and after 10 weeks of treatment. Surface antigens, cytokines and cellular molecules and the number of apoptotic cells will be analyzed by FACS, and the quantification of RNA will be analyzed by RT-PCR.
This will therefore enable us to study, before and after anti-TNF-α, in patients treated or not with azathioprine, on intestinal and blood lymphocytes, the production of cytokines involved in the lymphocyte-macrophage interaction, and the potential role of regulatory T cells.
Studietyp
Inskrivning (Förväntat)
Fas
- Inte tillämpbar
Kontakter och platser
Studieorter
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Nice, Frankrike, 06000
- Fédération des Maladies de l'appareil Digestif et de la Nutrition
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- patient older than 18
- social security
- active Crohn disease defined by a CDAI > 250
- sigmoïdal and/or rectal lesions
- requiring treatment by infliximab
- having never received any anti-TNF treatment
- a negative pregnancy test for women
- prescription of efficient contraception for women, having started at least a month before beginning the study, and throughout the duration of the study
- acceptance to participate in this research and having signed the consent form
- not participating in any other study
Exclusion Criteria:
- consent withdrawal
- the halt of infliximab treatment
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Grundläggande vetenskap
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Övrig: A
Patients with active Crohn disease and with azathioprine treatment
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rectosigmoïdal biopsies
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Övrig: B
Patient with active crohn disease and without azathioprine disease
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rectosigmoïdal biopsies
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
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Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells)
Tidsram: before treatment and 10 weeks after treatment
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before treatment and 10 weeks after treatment
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Sekundära resultatmått
Resultatmått |
Tidsram |
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Lymphocyte activation markers and macrophage activation markers
Tidsram: before treatment and 10 weeks after treatment
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before treatment and 10 weeks after treatment
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Samarbetspartners och utredare
Utredare
- Huvudutredare: Xavier Hébuterne, Professor, Centre Hospitalier Universitaire
Publikationer och användbara länkar
Allmänna publikationer
- Puntis J, McNeish AS, Allan RN. Long term prognosis of Crohn's disease with onset in childhood and adolescence. Gut. 1984 Apr;25(4):329-36. doi: 10.1136/gut.25.4.329.
- Rubin GP, Hungin AP, Kelly PJ, Ling J. Inflammatory bowel disease: epidemiology and management in an English general practice population. Aliment Pharmacol Ther. 2000 Dec;14(12):1553-9. doi: 10.1046/j.1365-2036.2000.00886.x.
- Arnott ID, Watts D, Satsangi J. Azathioprine and anti-TNF alpha therapies in Crohn's disease: a review of pharmacology, clinical efficacy and safety. Pharmacol Res. 2003 Jan;47(1):1-10. doi: 10.1016/s1043-6618(02)00264-5.
- ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease. Gut. 2002 Feb;50(2):206-11. doi: 10.1136/gut.50.2.206.
- MacDonald TT, Di Sabatino A, Gordon JN. Immunopathogenesis of Crohn's disease. JPEN J Parenter Enteral Nutr. 2005 Jul-Aug;29(4 Suppl):S118-24; discussion S124-5, S184-8. doi: 10.1177/01486071050290S4S118. Erratum In: JPEN J Parenter Enteral Nutr. 2006 Jan-Feb;30(1):table of contents. DiSabatino, Antonio [corrected to Di Sabatino, Antonio].
- Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity. 1994 Oct;1(7):553-62. doi: 10.1016/1074-7613(94)90045-0.
- Noguchi M, Hiwatashi N, Liu Z, Toyota T. Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease. Gut. 1998 Aug;43(2):203-9. doi: 10.1136/gut.43.2.203.
- Itoh J, de La Motte C, Strong SA, Levine AD, Fiocchi C. Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease. Gut. 2001 Jul;49(1):35-41. doi: 10.1136/gut.49.1.35.
- Baert FJ, D'Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, Geboes K, Rutgeerts PJ. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology. 1999 Jan;116(1):22-8. doi: 10.1016/s0016-5085(99)70224-6.
- Filippi J, Mambrini P, Arab K, Schneider SM, Hebuterne X. [Treatment of oesophageal Crohn's disease by infliximab]. Gastroenterol Clin Biol. 2005 Jan;29(1):84-5. doi: 10.1016/s0399-8320(05)80701-8. No abstract available. French.
- Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, Otsuka J, Okamura S, Fujita S, Harada M. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology. 2005 Feb;128(2):376-92. doi: 10.1053/j.gastro.2004.11.060.
- Agnholt J, Kaltoft K. Infliximab downregulates interferon-gamma production in activated gut T-lymphocytes from patients with Crohn's disease. Cytokine. 2001 Aug 21;15(4):212-22. doi: 10.1006/cyto.2001.0919.
- Lugering A, Schmidt M, Lugering N, Pauels HG, Domschke W, Kucharzik T. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology. 2001 Nov;121(5):1145-57. doi: 10.1053/gast.2001.28702.
- Danese S, Sans M, Scaldaferri F, Sgambato A, Rutella S, Cittadini A, Pique JM, Panes J, Katz JA, Gasbarrini A, Fiocchi C. TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease. J Immunol. 2006 Feb 15;176(4):2617-24. doi: 10.4049/jimmunol.176.4.2617.
- Filippi J, Roger PM, Schneider SM, Durant J, Breittmayer JP, Benzaken S, Bernard A, Dellamonica P, Hebuterne X; Groupe d'Etude Nicois Polyvalent en Infectiologie (GENPI). Infliximab and human immunodeficiency virus infection: Viral load reduction and CD4+ T-cell loss related to apoptosis. Arch Intern Med. 2006 Sep 18;166(16):1783-4. doi: 10.1001/archinte.166.16.1783. No abstract available.
- Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T, Nakamura T, Koganei K, Fukushima T, Watanabe M. CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol. 2004 Sep 1;173(5):3119-30. doi: 10.4049/jimmunol.173.5.3119.
- Kelsen J, Agnholt J, Hoffmann HJ, Romer JL, Hvas CL, Dahlerup JF. FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease. Clin Exp Immunol. 2005 Sep;141(3):549-57. doi: 10.1111/j.1365-2249.2005.02876.x.
- Ochsenkuhn T, Goke B, Sackmann M. Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease. Am J Gastroenterol. 2002 Aug;97(8):2022-5. doi: 10.1111/j.1572-0241.2002.05918.x.
- Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology. 2004 May;126(6):1593-610. doi: 10.1053/j.gastro.2004.02.070.
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 06 - PP - 2006
- 2006-006877-26
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