Ignite Creation Date:
2024-05-06 @ 7:48 AM
Last Modification Date:
2024-10-26 @ 11:52 AM
Study NCT ID:
NCT02604693
Status:
COMPLETED
Last Update Posted:
2021-04-29
First Post:
2015-11-10
Brief Title:
Exposure in Epigenetic Regulation of Immune Response in Chronic Beryllium Disease CBD
Sponsor:
National Jewish Health
Organization:
National Jewish Health
Study Overview
Official Title:
Exposure in Epigenetic Regulation of Immune Response in Chronic Beryllium
Status:
COMPLETED
Status Verified Date:
2021-04
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:
BeEpiGen
Brief Summary:
This study will provide important results for each aim while also providing an integrative transcriptional and epigenomic profile of CBD
In Aim 1 the Investigator will define genome-wide epigenetic alterations of CBD by determining genes that are DM in pivotal immune cells in the target organ CD4 BAL cells in CBD compared to BeS and healthy controls In addition the Investigator will determine the impact of Be exposure on the methylation profile of CBD and BeS cells compared to each other and normal controls This information will be used to define DM regions genes and their networks
Using the cases and controls from Aim 1 we will evaluate the gene-expression from these same subjects in Aim 2 to define functional epigenetic loci based on DE in CD4 BAL cells with and without Be exposure The Investigator will also integrate ENCODERE methylation histone modification and chromatin accessibility data as well as our genome-wide association study GWAS data to prioritize epigenetic marks and networks for confirmation and validation in Aim 3 In Aim 3 the Investigator will test the generalizability of their findings explore the potential of methylation marks as biomarkers of disease in PBMCs and determine if change in methylation of these targets with AZA or folic acid affects key immune and regulatory pathways in a second set of CBD and BeS subjects Throughout the Aims the Investigator will use both fresh CD4 T cells to directly assess disease relevance and Be-stimulated cultured CD4 T cells compared to unstimulated cultured T cells to assess the impact of environmental exposure
In Aim 1 the Investigator will define genome-wide epigenetic alterations of CBD by determining genes that are DM in pivotal immune cells in the target organ CD4 BAL cells in CBD compared to BeS and healthy controls In addition the Investigator will determine the impact of Be exposure on the methylation profile of CBD and BeS cells compared to each other and normal controls This information will be used to define DM regions genes and their networks
Using the cases and controls from Aim 1 we will evaluate the gene-expression from these same subjects in Aim 2 to define functional epigenetic loci based on DE in CD4 BAL cells with and without Be exposure The Investigator will also integrate ENCODERE methylation histone modification and chromatin accessibility data as well as our genome-wide association study GWAS data to prioritize epigenetic marks and networks for confirmation and validation in Aim 3 In Aim 3 the Investigator will test the generalizability of their findings explore the potential of methylation marks as biomarkers of disease in PBMCs and determine if change in methylation of these targets with AZA or folic acid affects key immune and regulatory pathways in a second set of CBD and BeS subjects Throughout the Aims the Investigator will use both fresh CD4 T cells to directly assess disease relevance and Be-stimulated cultured CD4 T cells compared to unstimulated cultured T cells to assess the impact of environmental exposure
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