Ignite Creation Date:
2024-05-06 @ 3:29 AM
Last Modification Date:
2024-10-26 @ 11:34 AM
Study NCT ID:
NCT02304666
Status:
UNKNOWN
Last Update Posted:
2015-08-31
First Post:
2014-11-27
Brief Title:
Study of Inflammatory Markers VNN1 in Crohn Disease and Ulcerative Colitis
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
Study of Inflammatory Markers VNN1 in Crohn Disease and Ulcerative Colitis
Status:
UNKNOWN
Status Verified Date:
2015-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
VANIN
Brief Summary:
Inflammatory Bowel diseases IBD include Crohns disease and ulcerative colitis IBDs precise origin is unknown until now Today the current hypothesis of the disease pathogenesis is that IBD result from a dysregulated mucosal immune response to the gut microbial flora in genetically susceptible hosts The intestinal homeostasis depends on interactions between immune and epithelial cells Epithelial cells are the first line of defense are tightly connected to the underlying gut associated lymphoid tissue and their alteration results in loss of tissue homeostasis
Vanin-1 Vnn1 in mice VNN1 in humans is an epithelial pantheinase which regulates the cell response to stress
This ectoenzyme hydrolyses the vitamin B5-derivative pantetheine to provide cysteamine to tissues and regenerate pantothenate Previous studies have shown that Vnn1 KO mice were more resistant to experimental colitis and administration of cystamine oxidized form of cysteamine restored their susceptibility to colitis Furthermore analysis of VNN1 expression in IBD patients show that high VNN1 expression is associated with severe clinical features Thus analysis of VNN1 expression could represent a good prognostic marker
In a recent published article we characterized among a retrospective cohort of 500 IBD patients and controls new SNPs single nucleotide polymorphisms in the VNN1 promoter and showed their association with IBD incidence and high VNN1 expression This suggested that the VNN1gene might be a new predisposition marker of IBD
In mouse Vnn1 expression is tightly regulated by activation of PPARa and PPARg transcription factors Interestingly one of the SNPs identified in patients participates to a PPARg binding site Interestingly drugs related to the family of 5-ASA which are commonly used in IBD have PPARgamma agonist potential Therefore quantifying VNN1 levels in patients under 5-ASA therapy might help predicting response to therapy and select patients with the highest benefit for this therapy
The purpose of this new project is to extend our initial analysis The study will be prospective monocentric and controlled Its primary objective is to evaluate the level of VNN1 expression in the colonic mucosa between IBD patients and control subjects to confirm the correlation between high VNN1 expression and IBD In relation with its prospective nature we will also try to associate VNN1 expression level with specific endophenotypes severity andor localization of the lesions quality of the response to therapy Finally we will screen patients for the previously identified SNPs to integrate this information in the interpretation of the results of expression analysis
This study is planned on 2 years Two groups of patients will be constituted one group will include IBD patients followed in the Service de Gastro-entérologie du Pr Grimaud à lHôpital Nord and the other group will constitute the control cohort including persons who were proposed a screening colonoscopy for familial history of colon cancer or polyps or for Irritable Bowel Syndrome
The investigator will have to fill a questionnaire for each included patient collecting information about age sex past medical history taken medicine digestive symptoms and colonoscopy indication
IBD patients will have a first set of biopsies n 10 and blood samples collected under general anesthesia during a colonoscopy planned in their IBD usual follow-up a second set of similar samples will be collected within the next 12 months if an endoscopic control is medically justified The control subjects will have only one set of biopsy and blood samples collected under general anesthesia during their colonoscopy In the particular case of IBD patients who require surgery a small piece of the resection will be collected ex-vivo on both healthy and pathologic areas
The blood sample will serve for quantification of the VNN1 seric pantheteinase activity and SNPs genetic study
The colonic biopsies will be obtained in duplicates from 5 different ileocolonic areas one for histopathological analysis and the other for transcriptional analysis by qRT-PCR
The surgical samples will be used for transcriptional activity tissue pantheteinase activity and constitution of TMA Tissue MicroArrays bank for immunohistochemistry
Expected benefits are to validate a new IBD prognostic marker for disease severity or potentially for evaluation of the therapeutic response
Vanin-1 Vnn1 in mice VNN1 in humans is an epithelial pantheinase which regulates the cell response to stress
This ectoenzyme hydrolyses the vitamin B5-derivative pantetheine to provide cysteamine to tissues and regenerate pantothenate Previous studies have shown that Vnn1 KO mice were more resistant to experimental colitis and administration of cystamine oxidized form of cysteamine restored their susceptibility to colitis Furthermore analysis of VNN1 expression in IBD patients show that high VNN1 expression is associated with severe clinical features Thus analysis of VNN1 expression could represent a good prognostic marker
In a recent published article we characterized among a retrospective cohort of 500 IBD patients and controls new SNPs single nucleotide polymorphisms in the VNN1 promoter and showed their association with IBD incidence and high VNN1 expression This suggested that the VNN1gene might be a new predisposition marker of IBD
In mouse Vnn1 expression is tightly regulated by activation of PPARa and PPARg transcription factors Interestingly one of the SNPs identified in patients participates to a PPARg binding site Interestingly drugs related to the family of 5-ASA which are commonly used in IBD have PPARgamma agonist potential Therefore quantifying VNN1 levels in patients under 5-ASA therapy might help predicting response to therapy and select patients with the highest benefit for this therapy
The purpose of this new project is to extend our initial analysis The study will be prospective monocentric and controlled Its primary objective is to evaluate the level of VNN1 expression in the colonic mucosa between IBD patients and control subjects to confirm the correlation between high VNN1 expression and IBD In relation with its prospective nature we will also try to associate VNN1 expression level with specific endophenotypes severity andor localization of the lesions quality of the response to therapy Finally we will screen patients for the previously identified SNPs to integrate this information in the interpretation of the results of expression analysis
This study is planned on 2 years Two groups of patients will be constituted one group will include IBD patients followed in the Service de Gastro-entérologie du Pr Grimaud à lHôpital Nord and the other group will constitute the control cohort including persons who were proposed a screening colonoscopy for familial history of colon cancer or polyps or for Irritable Bowel Syndrome
The investigator will have to fill a questionnaire for each included patient collecting information about age sex past medical history taken medicine digestive symptoms and colonoscopy indication
IBD patients will have a first set of biopsies n 10 and blood samples collected under general anesthesia during a colonoscopy planned in their IBD usual follow-up a second set of similar samples will be collected within the next 12 months if an endoscopic control is medically justified The control subjects will have only one set of biopsy and blood samples collected under general anesthesia during their colonoscopy In the particular case of IBD patients who require surgery a small piece of the resection will be collected ex-vivo on both healthy and pathologic areas
The blood sample will serve for quantification of the VNN1 seric pantheteinase activity and SNPs genetic study
The colonic biopsies will be obtained in duplicates from 5 different ileocolonic areas one for histopathological analysis and the other for transcriptional analysis by qRT-PCR
The surgical samples will be used for transcriptional activity tissue pantheteinase activity and constitution of TMA Tissue MicroArrays bank for immunohistochemistry
Expected benefits are to validate a new IBD prognostic marker for disease severity or potentially for evaluation of the therapeutic response
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2014-A01237-40 | OTHER | Ansm | None |