Crohn DiseaseNCT00561548
Impact of Anti-Tumor Necrosis Factor (TNF) Antibodies on the T-lymphocyte and Macrophage Cooperation in Crohn Disease
A study testing rectosigmoïdal biopsies in people with Crohn Disease, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- rectosigmoïdal biopsies
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- May 2007to Apr 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- consent withdrawal
- the halt of infliximab treatment
Trial locations and contacts
1 site in 1 country.
France1 site
Fédération des Maladies de l'appareil Digestif et de la Nutrition
Nice, 06000
About this study
Official title: Impact of Anti-TNF Antibodies on the T-lymphocyte and Macrophage Cooperation in the Crohn Disease
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.
Read the 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.
- Conditions
- Crohn Disease
- Being tested
- rectosigmoïdal biopsies
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rectosigmoïdal biopsiesProcedure or surgery
rectosigmoïdal biopsies
| Study group | Role | What they receive |
|---|---|---|
| A | Other | Patients with active Crohn disease and with azathioprine treatment Receives: Procedure: rectosigmoïdal biopsies |
| B | Other | Patient with active crohn disease and without azathioprine disease Receives: Procedure: rectosigmoïdal biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells)
Measured: before treatment and 10 weeks after treatment
Secondary outcomes (1)
Lymphocyte activation markers and macrophage activation markers
Measured: before treatment and 10 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2007 (estimated)
- Study startMay 2007
- Primary completionMay 2008
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Investigators
- Xavier Hébuterne, Professor, Principal investigator, Centre Hospitalier Universitaire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561548
- Sponsor's protocol ID
- 06 - PP - 2006
- Other IDs
- 2006-006877-26
- Status last verified
- Feb 2009
- First submitted
- 20 Nov 2007
- Last updated
- 30 May 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 6706211Rubin 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.
PubMed 11121902Arnott 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.
PubMed 12526855ten 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.
PubMed 11788561MacDonald 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.
PubMed 15980273Powrie 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.
PubMed 7600284Noguchi 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.
PubMed 10189845Itoh 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.
PubMed 11413108Baert 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.
PubMed 9869598Filippi 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.
PubMed 15738903Mitoma 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.
PubMed 15685549Agnholt 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.
PubMed 11563881Lugering 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.
PubMed 11677207Danese 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.
PubMed 16456024Filippi 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.
PubMed 16983059
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Anti-TNF Antibodies on the T-lymphocyte and Macrophage Cooperation in the Crohn Disease
- ClinicalTrials.gov ID
- NCT00561548
- Acronym / sponsor ID
- 06 - PP - 2006
- Conditions
- Crohn Disease
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- May 2008 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 21 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Other | Procedure: rectosigmoïdal biopsiesPatients with active Crohn disease and with azathioprine treatment |
| B | Other | Procedure: rectosigmoïdal biopsiesPatient with active crohn disease and without azathioprine disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- patient older than 18
- social security
- active Crohn disease defined by a CDAI > 250
- sigmoïdal and/or rectal lesions
- requiring treatment by infliximab
Key exclusion criteria (2 listed)
- consent withdrawal
- the halt of infliximab treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rectosigmoïdal biopsiesrectosigmoïdal biopsies | Procedure or surgery | A, B |
Primary outcome
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
1 secondary outcome
Lymphocyte activation markers and macrophage activation markers
Time frame: before treatment and 10 weeks after treatment
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2011.
- Background: PubMed 6706211Puntis 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.
- Background: PubMed 11121902Rubin 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.
- Background: PubMed 12526855Arnott 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.
- Background: PubMed 11788561ten 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.
- Background: PubMed 15980273MacDonald 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.
- Background: PubMed 7600284Powrie 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.
- Background: PubMed 10189845Noguchi 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.
- Background: PubMed 11413108Itoh 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.
- Background: PubMed 9869598Baert 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.
- Background: PubMed 15738903Filippi 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.
- Background: PubMed 15685549Mitoma 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.
- Background: PubMed 11563881Agnholt 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Hébuterne, Professor principal investigator
Centre Hospitalier Universitaire
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rectosigmoïdal biopsies in people with Crohn Disease, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00561548, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2011.