Ignite Creation Date:
2024-05-06 @ 1:39 AM
Last Modification Date:
2024-10-26 @ 11:07 AM
Study NCT ID:
NCT01862211
Status:
COMPLETED
Last Update Posted:
2018-11-07
First Post:
2013-05-22
Brief Title:
Polygen Defi-Alpha Genetic Polymorphisms Study in Children With Alpha-1 Antitrypsin Deficiency Included in the DEFI-ALPHA Cohort
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
POLYGEN DEFI-ALPHA Genetic Polymorphisms Study in Children With Alpha-1 Antitrypsin Deficiency Included in the DEFI-ALPHA Cohort
Status:
COMPLETED
Status Verified Date:
2018-11
Last Known Status:
None
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:
Polygen
Brief Summary:
The deficiency of alpha-1 antitrypsin DA1AT is a genetic disorder of variable clinical expression initially described in adults with pulmonary emphysema patients In children it is the second cause of neonatal cholestasis after biliary atresia and is a common indication for liver transplantation
Several genotypes for SERPINA1 gene coding for alpha-1 anti-trypsin were identified The main ones are M M M Z M S and Z Z and each genotype is closely correlated with the concentration of blood A1AT The estimate for France suggests a prevalence of genotype deficit Z Z of the order of 16054 9982 patients which in 11 of cases have liver disease prolonged neonatal jaundice Half of them will move towards the development of cirrhosis with portal hypertension at worst liver transplantation
Currently we do not know what are the clinical and genetic factors that predispose a patient A1AT deficiency develop liver damage Recent studies have led us to think that polymorphisms in the gene SERPINA1 as well as that of the alpha-mannosidase 1 endoplasmic reticulum Erman gene could be a predictive marker of liver complications Another possible candidate gene is one of the importin beta KPNB1 a protein involved in the elimination of misfolded proteins These data lead us to propose the study of genetic polymorphisms
The main objective of the study is to compare the allele frequencies of these polymorphisms between i a cohort of A1AT deficient patients and with hepatic symptoms portal hypertension and its complications severe liver failure leading to transplant or not or an indication for liver transplantation and ii a cohort of A1AT deficient patients without signs of hepatic call To build this last cohort we will include in the genetic study the family members of deficient patients some of whom probably carrying a deficit genotype Z Z but without any associated clinical manifestations This will allow us to facilitate the establishment of genotype profiles phenotype clearly identified which then allow a more appropriate care for children who may have such a development we will strive to achieve a haplotype interpretation of polymorphisms found
This study will be conducted in association with the DEFI-ALPHA study to identify clinical and biological prognostic factors such as age at diagnosis the diagnostic mode the results of liver biopsy when available the clinical course family history the existence of IUGR and long-term treatment
The secondary objectives of the study are
The measurement and interpretation of serum IL-8 in A1AT-deficient patients Indeed one study showed a higher IL-8 in patients with ulcerative colitis compared with healthy patients serum These considerations led us to hypothesize that IL-8 may be a marker of liver disease in A1AT deficiency
Preservation of blood samples for further study of other genes which may be in the future suspected to be associated with the occurrence of liver complications To this end a DNA bank will be created It will involve the children with a deficiency of alpha-1 antitrypsin and their family of 1st and 2nd degree in civil law parents and siblings
This study is a continuation of the cohort DEFI-ALPHA descriptive study of a cohort of children with DA1AT and sought to identify the clinical and biological factors such as age at diagnosis diagnosis mode the result sets of the liver biopsy when available clinical course family history the presence of IUGR and long-term treatment
The only criterion for not-inclusion is according to the subject the lack of consent of the child and his parents the lack of consent of the adult patient or the lack of consent of the witness Demographic and clinical history data for parents and brotherssisters showing no DA1AT will be collected
Currently the cohort of patients with DA1AT is being set up in the framework of the Cohort DEFI-ALPHA This multicenter project is realized with the help of french pediatric hepatology centers that regularly follow patients DA1AT Today over 100 patients DA1AT have already been identified and the collection of historical data has already begun on several centers since September 2009 This study is therefore a continuation of this work
Over a period of 30 months the total number of potentially includable subjects is estimated at about 400 in this study 100 patients and 300 related to the first degree such as parents brothers and sisters
This study will be promoted by the Hospices Civils de Lyon Authorization of the competent authority and the ethical committee will be obtained as well as informed consent from families before blood sampling
Several genotypes for SERPINA1 gene coding for alpha-1 anti-trypsin were identified The main ones are M M M Z M S and Z Z and each genotype is closely correlated with the concentration of blood A1AT The estimate for France suggests a prevalence of genotype deficit Z Z of the order of 16054 9982 patients which in 11 of cases have liver disease prolonged neonatal jaundice Half of them will move towards the development of cirrhosis with portal hypertension at worst liver transplantation
Currently we do not know what are the clinical and genetic factors that predispose a patient A1AT deficiency develop liver damage Recent studies have led us to think that polymorphisms in the gene SERPINA1 as well as that of the alpha-mannosidase 1 endoplasmic reticulum Erman gene could be a predictive marker of liver complications Another possible candidate gene is one of the importin beta KPNB1 a protein involved in the elimination of misfolded proteins These data lead us to propose the study of genetic polymorphisms
The main objective of the study is to compare the allele frequencies of these polymorphisms between i a cohort of A1AT deficient patients and with hepatic symptoms portal hypertension and its complications severe liver failure leading to transplant or not or an indication for liver transplantation and ii a cohort of A1AT deficient patients without signs of hepatic call To build this last cohort we will include in the genetic study the family members of deficient patients some of whom probably carrying a deficit genotype Z Z but without any associated clinical manifestations This will allow us to facilitate the establishment of genotype profiles phenotype clearly identified which then allow a more appropriate care for children who may have such a development we will strive to achieve a haplotype interpretation of polymorphisms found
This study will be conducted in association with the DEFI-ALPHA study to identify clinical and biological prognostic factors such as age at diagnosis the diagnostic mode the results of liver biopsy when available the clinical course family history the existence of IUGR and long-term treatment
The secondary objectives of the study are
The measurement and interpretation of serum IL-8 in A1AT-deficient patients Indeed one study showed a higher IL-8 in patients with ulcerative colitis compared with healthy patients serum These considerations led us to hypothesize that IL-8 may be a marker of liver disease in A1AT deficiency
Preservation of blood samples for further study of other genes which may be in the future suspected to be associated with the occurrence of liver complications To this end a DNA bank will be created It will involve the children with a deficiency of alpha-1 antitrypsin and their family of 1st and 2nd degree in civil law parents and siblings
This study is a continuation of the cohort DEFI-ALPHA descriptive study of a cohort of children with DA1AT and sought to identify the clinical and biological factors such as age at diagnosis diagnosis mode the result sets of the liver biopsy when available clinical course family history the presence of IUGR and long-term treatment
The only criterion for not-inclusion is according to the subject the lack of consent of the child and his parents the lack of consent of the adult patient or the lack of consent of the witness Demographic and clinical history data for parents and brotherssisters showing no DA1AT will be collected
Currently the cohort of patients with DA1AT is being set up in the framework of the Cohort DEFI-ALPHA This multicenter project is realized with the help of french pediatric hepatology centers that regularly follow patients DA1AT Today over 100 patients DA1AT have already been identified and the collection of historical data has already begun on several centers since September 2009 This study is therefore a continuation of this work
Over a period of 30 months the total number of potentially includable subjects is estimated at about 400 in this study 100 patients and 300 related to the first degree such as parents brothers and sisters
This study will be promoted by the Hospices Civils de Lyon Authorization of the competent authority and the ethical committee will be obtained as well as informed consent from families before blood sampling
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 |
|---|---|---|---|
| ID RCB | OTHER | 2012-A00204-39 | None |