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CIQTP Prolongation : Role and Mechanism in Sudden Cardiac Death

NCT03387072 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 394

Last updated 2021-03-17

No results posted yet for this study

Summary

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.

Conditions

Interventions

OTHER

Non interventional study

mental stress test and Blood (or salivary) sample

Sponsors & Collaborators

  • Nantes University Hospital

    lead OTHER

Principal Investigators

  • Jean-Baptiste GOURRAUD, Dr · Nantes University Hospital

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-03-14
Primary Completion
2021-03-16
Completion
2021-03-16

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03387072 on ClinicalTrials.gov