Ignite Creation Date:
2024-05-06 @ 7:38 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06087367
Status:
RECRUITING
Last Update Posted:
2024-04-12
First Post:
2023-10-12
Brief Title:
Building of a DiagnosticPrognostic Database for Human ERG Variant Effects
Sponsor:
Nantes University Hospital
Organization:
Nantes University Hospital
Study Overview
Official Title:
Building of a DiagnosticPrognostic Database by High-throughput Multiplexed Assays for Human ERG Variant Effects
Status:
RECRUITING
Status Verified Date:
2023-10
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:
CarDiag
Brief Summary:
Cardiac channelopathies induce severe heart rhythm or conduction disorders Mutations of the KCNH2 gene that encodes the human h ERG channel is responsible for 30-40 of all cases of long QT syndrome inherited LQT2 Besides hERG is frequently responsible for off-target effects of several pharmacological agents acquired LQT2 With the advent of Next Generation Sequencing hundreds of new KCNH2 variants are accumulating in regional databases including those developed by french centers of references Worldwide we estimate there are more than 1000 variants for hERG channel Unfortunately many of these new variants appear to be of unknown functional significance in spite of available clinical and genetic information Little is known on whether they affect the channel biophysical properties its expression at the cell surface andor its structure Yet this information is crucial to determine the real degree of pathogenicity of these variants and therefore to make the proper diagnosis on inherited LQT2 counsel the patient for his treatment and improve the management of the patients life Our ambition is therefore to tackle this issue of variant significance by i launching a large-scale multi-functional evaluation of hERG variants ii introducing for the first time a formatted large-scale pathogenicity annotation score for all variants that have been functionally evaluated by this multi-parametric approach and iii regrouping all the relevant information collected in every French Regional centers of reference into a single National database hosted by an infrastructure that possesses enough flexibility for continuous data implementation and cross-referencing The database will integrate the latest International guidelines for functional pathogenicity annotation This project will also include the pharmacological characterization of several drugs susceptible to produce acquired LQT2 with variable severities We aim to understand whether there are structural regions within hERG channel in which the introduction of a variant is more prone to increase the risk of acquired LQT2 or if on the contrary a set of variants may relatively protect some patients against LQT2-inducing drugs
Detailed Description:
None
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?:
None
Is an FDA AA801 Violation?:
None