NCT00561548

Brief Summary

The aim of this research is to study Crohn disease patients before and after anti-TNF, the cooperation between lamina propria T-lymphocytes and macrophages, through the expression of co-signalisation molecules and their ligands, the production of cytokines participating in this cooperation, and the potential role of regulatory T lymphocytes.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started May 2007

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2007

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

November 20, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 21, 2007

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2008

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
Last Updated

May 30, 2011

Status Verified

February 1, 2009

Enrollment Period

1 year

First QC Date

November 20, 2007

Last Update Submit

May 27, 2011

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

  • Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells)

    before treatment and 10 weeks after treatment

Secondary Outcomes (1)

  • Lymphocyte activation markers and macrophage activation markers

    before treatment and 10 weeks after treatment

Study Arms (2)

A

OTHER

Patients with active Crohn disease and with azathioprine treatment

Procedure: rectosigmoïdal biopsies

B

OTHER

Patient with active crohn disease and without azathioprine disease

Procedure: rectosigmoïdal biopsies

Interventions

rectosigmoïdal biopsiesPROCEDURE

rectosigmoïdal biopsies

AB

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • consent withdrawal
  • the halt of infliximab treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fédération des Maladies de l'appareil Digestif et de la Nutrition

Nice, 06000, France

Location

Related Publications (19)

  • 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.

    PMID: 6706211BACKGROUND

  • 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.

    PMID: 11121902BACKGROUND

  • 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.

    PMID: 12526855BACKGROUND

  • 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.

    PMID: 11788561BACKGROUND

  • 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.

    PMID: 15980273BACKGROUND

  • 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.

    PMID: 7600284BACKGROUND

  • 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.

    PMID: 10189845BACKGROUND

  • 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.

    PMID: 11413108BACKGROUND

  • 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.

    PMID: 9869598BACKGROUND

  • 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.

    PMID: 15738903BACKGROUND

  • 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.

    PMID: 15685549BACKGROUND

  • 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.

    PMID: 11563881BACKGROUND

  • 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.

    PMID: 11677207BACKGROUND

  • 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.

    PMID: 16456024BACKGROUND

  • 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.

    PMID: 16983059BACKGROUND

  • 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.

    PMID: 15322172BACKGROUND

  • 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.

    PMID: 16045746BACKGROUND

  • 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.

    PMID: 12190171BACKGROUND

  • 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.

    PMID: 15168370BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel DiseasesGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Study Officials

  • Xavier Hébuterne, Professor

    Centre Hospitalier Universitaire

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

November 20, 2007

First Posted

November 21, 2007

Study Start

May 1, 2007

Primary Completion

May 1, 2008

Study Completion

April 1, 2009

Last Updated

May 30, 2011

Record last verified: 2009-02

Locations

FR(1)