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Report for Clinical Trial NCT03387072

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

CIQTP Prolongation : Role and Mechanism in Sudden Cardiac Death

Despite major progress in molecular and phenotypic characterization of primary electrical disorders, many (aborted) sudden cardiac deaths (SCD) occur in young victims without identifiable abnormalities. Investigator recently identified, in 4 families presenting unexplained SCD, a new arrhythmia entity (catecholamine-induced QT prolongation; CIQTP) characterized by normal QT duration at rest but major QT lengthening during mental stress test (MST). Investigators aim to determine the prevalence of this new phenotype in unexplained SCD and identify its underlying pathophysiological mechanism. More specifically, investigators aim to: - determine the prevalence of CIQTP in unexplained SCD and identify new affected families; - identify the role of mental stress in QT prolongation; - identify the genetics basis underlying this life threatening disease; - perform transcriptomic and electrophysiological profiling of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from CIQTP patients to identify putative biomarkers and pathophysiological mechanisms. MST will be performed, additionally to the conventional screening, in families affected by unexplained SCD or long QT syndrome (LQTS) referred to university hospitals of Nantes, Rennes, Tours and Brest. Relevance of the MST on the different type of LQTS will be evaluated and compared to conventional provocative tests (epinephrine, exercise). Whole-genome sequencing will first be performed in 3 distantly affected relatives within each of the 4 largest families identified. As previously performed in Nantes, analysis of the shared rare variants will allow identifying gene(s) associated with the disease. Transcriptomic (high-throughput 3' Digital Gene Expression mRNA sequencing) and electrophysiological (96-well automated optical recordings of action potentials and patch-clamp recordings of ionic currents, using specific ion channel activators and inhibitors) profiling will be performed on iPSC-CMs from 2 affected and one unaffected first-degree relatives of these 4 large families.

NCT03387072 Sudden Cardiac Death
MeSH:Death, Sudden, Cardiac Death
HPO:Sudden cardiac death

1 Interventions

Name: Non interventional study

Description: mental stress test and Blood (or salivary) sample
Type: Other
Group Labels: 3

Healthy relatives of patients affected with CIQTP Patients affected w Patients affected with CIQTP

Primary Outcomes

Measure: Number of families diagnosed with a CIQTP syndrome compared to the number of families who underwent a familial screening after a sudden cardiac death

Time: 12 months

Secondary Outcomes

Measure: Identification of genetics variants involved in the occurrence of CIQTP syndrome

Time: 24 months

Measure: gene and ionic current expression modifications between healthy and affected relatives

Time: 24 months

Time Perspective: Prospective


There is one SNP


1 A561P

Regarding the iPS cells from the LQT2 patient, the investigators showed that hERG A561P mutation leads to a trafficking defect that results in reduced IKr current, and consequently e to action potential prolongation and cellular arrhythmias(early afterdepolarizations) . --- A561P ---

HPO Nodes