Impact of Anti-Tumor Necrosis Factor (TNF) Antibodies on the T-lymphocyte and Macrophage Cooperation in Crohn Disease

This study has been terminated.
Sponsor:
Information provided by:
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT00561548
First received: November 20, 2007
Last updated: May 27, 2011
Last verified: February 2009
  Purpose

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.


Condition Intervention
Crohn Disease
Procedure: rectosigmoïdal biopsies

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Impact of Anti-TNF Antibodies on the T-lymphocyte and Macrophage Cooperation in the Crohn Disease

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells) [ Time Frame: before treatment and 10 weeks after treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Lymphocyte activation markers and macrophage activation markers [ Time Frame: before treatment and 10 weeks after treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2007
Study Completion Date: April 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A
Patients with active Crohn disease and with azathioprine treatment
Procedure: rectosigmoïdal biopsies
rectosigmoïdal biopsies
B
Patient with active crohn disease and without azathioprine disease
Procedure: rectosigmoïdal biopsies
rectosigmoïdal biopsies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00561548

Locations
France
Fédération des Maladies de l'appareil Digestif et de la Nutrition
Nice, France, 06000
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Principal Investigator: Xavier Hébuterne, Professor Centre Hospitalier Universitaire
  More Information

Publications:

Responsible Party: Département de la Recherche Clinique et de l'Innovation, CHU de Nice
ClinicalTrials.gov Identifier: NCT00561548     History of Changes
Other Study ID Numbers: 06 - PP - 2006, 2006-006877-26
Study First Received: November 20, 2007
Last Updated: May 27, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority
France: Institutional Ethical Committee

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on April 17, 2014