Ignite Creation Date:
2024-05-06 @ 8:03 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06231498
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-23
First Post:
2023-11-14
Brief Title:
The Epigenomic Signature of Eosinophilic Granulomatosis With Polyangiitis
Sponsor:
Meyer Childrens Hospital IRCCS
Organization:
Meyer Childrens Hospital IRCCS
Study Overview
Official Title:
Disease Susceptibility and Response to IL5 Blockade in Patients With Eosinophilic Granulomatosis With Polyangiitis EGPA an Epigenome-wide Association Study Integrated With Transcriptomic and Proteomic Analyses
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
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:
EPI-EGPA
Brief Summary:
This is a case-control observational study on blood samples The primary goal of this study is to identify the epigenetic marks that can distinguish patients suffering from Eosinophilic Granulomatosis with Polyangiitis EGPA from healthy individuals The secondary goal is to identify epigenetic or transcriptional marks that can predict if a patient with EGPA will benefit from therapy with Mepolizumab This study is observational meaning there will be no alterations of patients routine clinical care A blood sample will be drawn for each patient If the patient will undergo treatment with Mepolizumab based on routine clinical care then the blood sample will be drawn before Mepolizumab initiation The blood samples will be used for genome-wide DNA methylation profiling and for transcriptomic profiling Healthy individuals as controls for the association study will not be recruited In fact the epigenetic and transcriptomic data obtained from EGPA patient blood will be compared against already available genome-wide DNA methylation and transcriptomic profiles of the blood of healthy individuals from previous studies A total of 300 patients with EGPA will be recruited for the study The first part of the study corresponding to the primary goal will involve all of the 300 patients The second part of the study corresponding to the secondary goal will involve a study population subset consisting of 50 patients
Detailed Description:
Background and Rationale Eosinophilic Granulomatosis with Polyangiitis EGPA is a rare multisystem immune-mediated disease classified both among Anti Neutrophil Cytoplasmic Antibody ANCA-associated vasculitis and among hypereosinophilic disorders Current scientific knowledge describes EGPA as a complex or multifactorial nature of the disease ie the disease is triggered by a combination of inherited genetic variants and environmental factors The term epigenetics refers to heritable alterations in gene expression which do not correspond to a variation in the underlying DNA sequence In the context of various autoimmune diseases similar to EGPA and in the context of asthma a condition that almost all EGPA patients suffer from several studies have highlighted that epigenetics plays a fundamental role in the pathogenesispathophysiology and that in particular it can potentially represent the mechanism by which environmental exposures interact with genetics to cause the disease Therefore studying epigenetics and namely DNA methylation as the most studied epigenetic mechanism in EGPA could lead to an in-depth knowledge of the pathology and in particular to the identification of epigenetic markers useful in diagnosis or in monitoring disease activity or in predicting response to pharmacological treatment
Objectives The primary objective is the identification of loci whose methylation level is associated with the pathology ie epigenetic markers of the disease The secondary objectives are identification of loci whose methylation level correlates with the response to treatment with the drug Mepolizumab in patients affected by the disease ie epigenetic markers predictive of response to Mepolizumab identification of genes whose transcription level is related to the disease and of proteins whose plasma concentration is related to the disease in this way we expect to evaluate the effects of epigenetic variation on geneprotein expression and to identify the corresponding biological pathways identification of epigenetic predictors of disease outcomes eg remission relapse survival identification of epigenetic markers of the main disease subphenotypes ie the ANCA and ANCA- subsets
Study Design Observational case-control study on biological samples The study is divided into two different parts The first part is a genome-wide DNA methylation case-control association study The genome-wide methylation profile derived from blood samples from 300 patients will be compared to the methylation profile in the blood of healthy individuals The second part is a predictive study aiming at assessing whether epigenetics can be used to predict the response to Mepolizumab This part of the study will cover a study population subset consisting of 50 patients who will undergo treatment with Mepolizumab as part of their clinical routine and whose blood sample will be drawn before starting Mepolizumab therapy Not only the genome-wide methylation profile will be obtained from the blood like all the other patients included in the study but also the transcriptomic profile These profiles will be analyzed to search for loci whose level of methylation andor expression correlate with the response to treatment with Mepolizumab
Objectives The primary objective is the identification of loci whose methylation level is associated with the pathology ie epigenetic markers of the disease The secondary objectives are identification of loci whose methylation level correlates with the response to treatment with the drug Mepolizumab in patients affected by the disease ie epigenetic markers predictive of response to Mepolizumab identification of genes whose transcription level is related to the disease and of proteins whose plasma concentration is related to the disease in this way we expect to evaluate the effects of epigenetic variation on geneprotein expression and to identify the corresponding biological pathways identification of epigenetic predictors of disease outcomes eg remission relapse survival identification of epigenetic markers of the main disease subphenotypes ie the ANCA and ANCA- subsets
Study Design Observational case-control study on biological samples The study is divided into two different parts The first part is a genome-wide DNA methylation case-control association study The genome-wide methylation profile derived from blood samples from 300 patients will be compared to the methylation profile in the blood of healthy individuals The second part is a predictive study aiming at assessing whether epigenetics can be used to predict the response to Mepolizumab This part of the study will cover a study population subset consisting of 50 patients who will undergo treatment with Mepolizumab as part of their clinical routine and whose blood sample will be drawn before starting Mepolizumab therapy Not only the genome-wide methylation profile will be obtained from the blood like all the other patients included in the study but also the transcriptomic profile These profiles will be analyzed to search for loci whose level of methylation andor expression correlate with the response to treatment with Mepolizumab
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None