Clinical trial NCT01338441: Selections of Subjects With Important Changes in Their Cardiac Repolarization Parameters for the Procurement of Skin and Blood Samples
Official title: Selections of Subjects With Dramatic Changes in Their Cardiac Repolarization Parameters After a Pharmacologic Stimulus Aiming to Collect Their Skin Biopsy and Blood Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiology: RR / QT
Keywords: Drug induced QT prolongation
Lead sponsor: Ectycell SASU
Sponsor class: INDUSTRY
Collaborators: name: Pierre and Marie Curie University
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2011-04-19
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The study main objective is to assess the changes in the ventricular repolarization (measure by the delta QTcf) after drug induced stimulation, compare to placebo, in order to identify subjects with extreme responses and collecting their skin and blood samples.

Detailed description: An ECG is performed after a dose of sotalol on about 100 healthy subjects in order to identify about 20 extreme responders (10 high responders and 10 non responders) assessed as Delta QTcf compare to baseline. The ECG will be measured and the delta QTcf will be calculated on the 20 selected subjects in a second part of the clinical trial, cross over erythromycin/placebo.

Eligibility criteria: Inclusion Criteria:

* 18 to 40 years of age
* Caucasian origin
* BMI 19 to 29 kg/m²
* Informed Consent obtained
* National Health Security Number
* Eligible for Phase I as mentioned in the national registry of healthy volunteers
* For woman: use of an effective contraceptive method

Non Inclusion Criteria:

* Asthma
* Heart Rate \< 50 bpm
* Hypotension with systolic blood pressure\< 100 mm Hg.
* atrioventricular block (PR interval \> 200 ms)
* Known Chronic illness (hepatic, renal or cardiac impairment, etc..)
* Raynaud's phenomenon
* Drug known to prolong QT (http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) in the last 7 days.
* All chronic treatments are forbidden exceptive : oral contraceptives, paracetamol, vitamins and comfort treatment that do not prolong the QT
* Known family or individual past history of QT prolongation or unexplained syncope
* (QTcF) \> 450 ms
* QRS interval non assessable on ECG at rest or bundle-branch block, QRS \> 100 ms
* Allergy to macrolide type antibiotics
* Known allergy to sotalol or lidocaine
* Positive blood pregnancy test (Inclusion visit)
* Known abnormal haemostasis
* Kaliemia\< 3.5 mmol/L
* Magnesemia\< 0,7 mmol/L
* Under exclusion period or participating to another clinical trial on a new medicinal product
* Creatinin clearance \< 80 ml/min (Cockroft and Gault formula)
* AST-ALT \>3x upper normal limit

Primary outcomes:
measure: Prolongation of cardiac QT due to erythromycin compare to Placebo reported as Delta QTcf
timeFrame: 1hour and 20 minutes
Secondary outcomes:
measure: Comparison Delta QTcf eryhtromycin-sotalol
timeFrame: over 3 hours
measure: Assess the effect of erythromycin Twave morphologie changes
timeFrame: 1hour and 20 min
Other outcomes:
Locations:
city: Rueil Malmaison
country: France
facility: BIOTRIAL
Study officials:
affiliation: University PMCurrie-INSERM
name: Jean Sebastien Hulot, MD
role: STUDY_DIRECTOR
References:
citation: Stillitano F, Hansen J, Kong CW, Karakikes I, Funck-Brentano C, Geng L, Scott S, Reynier S, Wu M, Valogne Y, Desseaux C, Salem JE, Jeziorowska D, Zahr N, Li R, Iyengar R, Hajjar RJ, Hulot JS. Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells. Elife. 2017 Jan 30;6:e19406. doi: 10.7554/eLife.19406.