Clinical trial NCT00773201: Genetic Sources of Variability of the Adaptation of the Ventricular Repolarisation
Official title: Identification of the Genetic Sources of Variability of the Adaptation of the Ventricular Repolarisation at a Pharmacological and Physiological Stimulus in an Apparently Normal Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Long QT syndrome
Cardiac repolarisation
Genome-wide association
Electrophysiology
Drugs/adverse effects
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-10-16
Enrollment: 997
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective is to research for genetic factors involved in the extreme modifications of the QT interval of the electrocardiogram in answer to a pharmacological stimulation (sotalol) and physiological stimulation in the apparently normal general population.

The phenotypic characterization, based on the ventricular repolarisation dynamics will be used aiming at term of the predictive genetic factors of the acquired long QT syndrome

Detailed description: Study of 1000 apparently healthy subjects which will receive an unique dose of Sotalol and will have an effort test on ergonomic bicycle, an auditive stimulation and a taking of DNA.

Eligibility criteria: Inclusion Criteria:

* Both sexes
* Age between 18 and 60 years
* European or North African Origin
* Body mass index between 19 and 29 kg / m ²
* Obtaining informed and written consent

Exclusion Criteria:

* Asthma
* Heart rate \< 50 bpm
* Systolic blood pressure \< 100 mm Hg
* Atrioventricular block
* Known chronic illness with chronic treatment
* Raynaud phenomenon
* QT prolonging drug
* Family or personal history of the congenital long QT syndrome
* QT/QTc Fridericia (QTcf) \> 450 ms
* Pregnancy

Primary outcomes:
measure: The elongation of the corrected interval QT duration 3 hours after the unique oral taking of an 80 mg dose of Sotalol.
timeFrame: 3 hours after the taking of Sotalol
Secondary outcomes:
measure: Constitute a biological base and a phenotypic base of resources which will allow to define answer phenotypes to the implemented dynamic tests
timeFrame: At the inclusion visit
measure: Look for associations between these phenotypes of electrocardiographically answer and mutations or polymorphisms.
timeFrame: At the inclusion visit
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre d'investigation clinique; Hôpital Saint Antoine
Study officials:
affiliation: Hôpital Saint Antoine, Assistance Publique - Hopitaux de Paris
name: Beny Charbit, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Salem JE, Germain M, Hulot JS, Voiriot P, Lebourgeois B, Waldura J, Tregouet DA, Charbit B, Funck-Brentano C. GENomE wide analysis of sotalol-induced IKr inhibition during ventricular REPOLarization, "GENEREPOL study": Lack of common variants with large effect sizes. PLoS One. 2017 Aug 11;12(8):e0181875. doi: 10.1371/journal.pone.0181875. eCollection 2017.