Crohn Disease-Associated Colorectal AdenocarcinomaP2RX7NCT02293811
Decoding of the Expression of Tumor Suppressor P2RX7 in Inflammatory and Malignant Colonic Mucosa
A study testing Analysis in people with Crohn Disease-Associated Colorectal Adenocarcinoma, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial summary
The inflammatory tumor micro-environment is a consequence and a driver of tumorogenesis. On one hand it promotes antitumor immune responses and on the other hand it favors development and progression of cancerous lesions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease-Associated Colorectal Adenocarcinoma
- What is being tested?
- Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 9 Feb 2015to 15 Dec 2015
- 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
- · All the patients requiring an endoscopy within the framework of a colorectal cancer
- All the patients requiring a low digestive endoscopy within the framework of the diagnosis or of the follow-up of a colorectal cancer, realized in the CHU of Nice.
- Realization of a preliminary medical examination
- Obligation for all the patients to be affiliated to the Social Security
- Signature of the informed consent
Who cannot join
- • Pushed acute severe of the disease defined by the score of Truelove and Witss or the score of Lichtiger > 10 (cf appendix)
- severe endoscopic Hurts returning the practice of dangerous additional biopsies
- Disorders of the coagulation or the patient under anti-vitamin K, aspirin or clopidogrel.
- Patient presenting an unchecked renal, respiratory, hepatic or cardiac insufficiency
- Patient known positive HIV
- vulnerable People: pregnant or breast-feeding women (a pregnancy test will be realized), minors, adults under guardianship or guardianships, deprived of freedom
Trial locations and contacts
1 site in 1 country.
About this study
The inflammatory tumor micro-environment is a consequence and a driver of tumorogenesis. On one hand it promotes antitumor immune responses and on the other hand it favors development and progression of cancerous lesions.
Factors regulating the complex interplay between epithelial and immune cells are still poorly characterized. Extracellular ATP (eATP) acting on the purinergic P2X7 receptors (P2RX7) has recently emerged as a key signaling pathway in the immune response.
Read more
Recent data have revealed the crucial role of P2RX7-NLRP3-Caspase-1 for priming dendritic cells (DC) within the tumor microenvironment upon treatment with certain types of chemotherapy drugs. Despite this important discovery, no previous study has so far investigated the global in vivo effect of P2RX7 modulation in inflammation-induced carcinogenesis of mucosal tissues.
Our consortium, endowed by a long standing experience in the field of mucosal immunology, inflammation and signaling, already demonstrated that the P2RX7 is differentially expressed in the mucosa of patients with active and quiescent inflammatory bowel disease (IBD), where eATP is present at very high concentration, and that P2RX7 controls an amplification loop of the inflammatory response (Cesaro et al., 2010). Furthermore, we uncovered that P2RX7 controls homeostasis, survival and function of regulatory T cells (Hubert et al., 2010). In addition, our recent demonstration that P2RX7 deficiency lowered mucosal inflammation but unexpectedly enhanced tumor formation in vivo warrants additional efforts to explore the molecular and cellular mechanisms accounting for this effect and suggest that enhancing P2RX7 function may have an anti-tumor therapeutic effect.
These observations emphasize the tumor suppressor role of P2X7 receptor, warrant further investigation to better understand the molecular mechanisms responsible for this anti-tumor effect and suggest that enhancing the function of P2X7R could have a therapeutic effect significant antitumor.
Our main objectives is to explore the role of P2RX7 in healthy, inflammatory and cancerous colonic mucosa. For this we will map the expression of the protein P2RX7 and realize genotype of P2RX7 forms in inflammatory diseases and cancer of the colon.
- Being tested
- Analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnalysisOther
An additional blood sample (10ml) will be taken on the day of hospitalization to achieve the genomic studies in search of mutations in constitutional DNA of circulating lymphocytes and acquired mutations of DNA circulating.
We will use the technique of tissue-microarray to analyze the expression level of P2RX7 both in epithelial cells than in stromal cells inflammatory.
Genotyping will be conducted partly on colonic biopsies and also on blood samples (to demonstrate the feasibility of this technique much less debilitating).
| Study group | Role | What they receive |
|---|---|---|
| biopsy | Other | We will use colonic biopsies performed in the gastroenterology after obtaining consent from the patient and the agreement of the committee for the protection of persons. 5 biopsy will be performed for all patients except those with colon cancer for xhich we realize only 3 colonic biopsy (1 in healthy area and 2 in cancerous area )
To obtain statistically significant results we will establish the following six study groups, as far as possible matched for age and sex:
* healthy patients;
* patients with colonic Crohn disease in acute phase;
* patients with colonic Crohn disease in chronic phase;
* patients with ulcerative colitis in acute phase;
* patients with ulcerative colitis in chronic phase;
* patients with colon cancer Receives: Other: Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of expression of P2RX7
The evaluation of the level of expression of P2RX7 will realized by tissue microarray (TMA). TMA is produced using colonic biopsies fixed in 10% formalin. Plug of paraffin embedded tissue will be selected from stained with hematoxylin eosin saffron corresponding cuts. This selection of the tissue area taken from the donor block must be done carefully, conditioning the quality of the "array". In practice, for each patient, 3 Plug of 0.6 mm shall be taken from a biopsy performed in pathological tissue. A total of 156 spots TMA of 0.6 mm diameter plug shall be included according to a pre-established in a receiver block plane (consisting of virgin paraffin).
Measured: One time
Secondary outcomes (1)
Five isoforms of the P2RX7 protein
Five isoforms of the P2RX7 protein are described and each of its isoforms have many single nucleotide polymorphisms (SNPs). Among the 1754 mutations identified, 33 have been referenced in Pubmed publications and 4 are associated with diseases such as osteoarthritis, chronic pain and leukemias. Thus, the function of P2X7R may be affected by the expression of variants "gain of function" or "loss of function" and it is important to map the expression of these variants to anderstand the role of P2X7R in inflammatory bowel diseases and colonic cancer.
Genotyping will be conducted on colonic biopsy and on blood samples (to demonstrate the feasibility of this technique much less debilitating). We will use the platform MassARRAY SNP multiplex (present in my home lab) by following the procedures established by the platform.
Measured: one time
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study start9 Feb 2015
- Primary completion15 Oct 2015
- Study completion15 Dec 2015
Why it stopped: the tissue mass of each biopsy sample was not sufficient to perform an exploratory analysis to assess the level of expression of the P2RX7 protein.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn Disease-Associated Colorectal AdenocarcinomaStudies 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- HEBUTERNE Xavier, PhD, Principal investigator, CHU de Nice, Hôpital Archet, Gastroentérologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293811
- Sponsor's protocol ID
- 14-AOI-04
- Acronym
- P2RX7
- Status last verified
- Mar 2024
- First submitted
- 14 Nov 2014
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decoding of the Expression of Tumor Suppressor P2RX7 in Inflammatory and Malignant Colonic Mucosa
- ClinicalTrials.gov ID
- NCT02293811
- Acronym / sponsor ID
- P2RX7 / 14-AOI-04
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: the tissue mass of each biopsy sample was not sufficient to perform an exploratory analysis to assess the level of expression of the P2RX7 protein.
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 9 Feb 2015 (actual)
- Primary completion
- 15 Oct 2015 (actual)
- Study completion
- 15 Dec 2015 (actual)
- First posted
- 18 Nov 2014 (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 inflammatory tumor micro-environment is a consequence and a driver of tumorogenesis. On one hand it promotes antitumor immune responses and on the other hand it favors development and progression of cancerous lesions.
Factors regulating the complex interplay between epithelial and immune cells are still poorly characterized. Extracellular ATP (eATP) acting on the purinergic P2X7 receptors (P2RX7) has recently emerged as a key signaling pathway in the immune response.
Recent data have revealed the crucial role of P2RX7-NLRP3-Caspase-1 for priming dendritic cells (DC) within the tumor microenvironment upon treatment with certain types of chemotherapy drugs. Despite this important discovery, no previous study has so far investigated the global in vivo effect of P2RX7 modulation in inflammation-induced carcinogenesis of mucosal tissues.
Our consortium, endowed by a long standing experience in the field of mucosal immunology, inflammation and signaling, already demonstrated that the P2RX7 is differentially expressed in the mucosa of patients with active and quiescent inflammatory bowel disease (IBD), where eATP is present at very high concentration, and that P2RX7 controls an amplification loop of the inflammatory response (Cesaro et al., 2010). Furthermore, we uncovered that P2RX7 controls homeostasis, survival and function of regulatory T cells (Hubert et al., 2010). In addition, our recent demonstration that P2RX7 deficiency lowered mucosal inflammation but unexpectedly enhanced tumor formation in vivo warrants additional efforts to explore the molecular and cellular mechanisms accounting for this effect and suggest that enhancing P2RX7 function may have an anti-tumor therapeutic effect.
These observations emphasize the tumor suppressor role of P2X7 receptor, warrant further investigation to better understand the molecular mechanisms responsible for this anti-tumor effect and suggest that enhancing the function of P2X7R could have a therapeutic effect significant antitumor.
Our main objectives is to explore the role of P2RX7 in healthy, inflammatory and cancerous colonic mucosa. For this we will map the expression of the protein P2RX7 and realize genotype of P2RX7 forms in inflammatory diseases and cancer of the colon.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| biopsy | Other | Other: AnalysisWe will use colonic biopsies performed in the gastroenterology after obtaining consent from the patient and the agreement of the committee for the protection of persons. 5 biopsy will be performed for all patients except those with colon cancer for xhich we realize only 3 colonic biopsy (1 in healthy area and 2 in cancerous area ) To obtain statistically significant results we will establish the following six study groups, as far as possible matched for age and sex: * healthy patients; * patients with colonic Crohn disease in acute phase; * patients with colonic Crohn disease in chronic phase; * patients with ulcerative colitis in acute phase; * patients with ulcerative colitis in chronic phase; * patients with colon cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- · All the patients requiring an endoscopy within the framework of a colorectal cancer
Key exclusion criteria (6 listed)
- • Pushed acute severe of the disease defined by the score of Truelove and Witss or the score of Lichtiger > 10 (cf appendix)
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 |
|---|---|---|
| AnalysisAn additional blood sample (10ml) will be taken on the day of hospitalization to achieve the genomic studies in search of mutations in constitutional DNA of circulating lymphocytes and acquired mutations of DNA circulating. We will use the technique of tissue-microarray to analyze the expression level of P2RX7 both in epithelial cells than in stromal cells inflammatory. Genotyping will be conducted partly on colonic biopsies and also on blood samples (to demonstrate the feasibility of this technique much less debilitating). | Other | biopsy |
Primary outcome
Analysis of expression of P2RX7
Time frame: One time
The evaluation of the level of expression of P2RX7 will realized by tissue microarray (TMA). TMA is produced using colonic biopsies fixed in 10% formalin. Plug of paraffin embedded tissue will be selected from stained with hematoxylin eosin saffron corresponding cuts. This selection of the tissue area taken from the donor block must be done carefully, conditioning the quality of the "array". In practice, for each patient, 3 Plug of 0.6 mm shall be taken from a biopsy performed in pathological tissue. A total of 156 spots TMA of 0.6 mm diameter plug shall be included according to a pre-established in a receiver block plane (consisting of virgin paraffin).
1 secondary outcome
Five isoforms of the P2RX7 protein
Time frame: one time
Results and safety
The study was stopped early (reason given: the tissue mass of each biopsy sample was not sufficient to perform an exploratory analysis to assess the level of expression of the P2RX7 protein.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
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.
HEBUTERNE Xavier, PhD principal investigator
CHU de Nice, Hôpital Archet, Gastroentérologie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Analysis in people with Crohn Disease-Associated Colorectal Adenocarcinoma, 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 5 inclusion and 6 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 18 Mar 2024. 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 (reason given: the tissue mass of each biopsy sample was not sufficient to perform an exploratory analysis to assess the level of expression of the P2RX7 protein.). 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?
Analysis of expression of P2RX7 (time frame: One time). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Mar 2024.