Selections of Subjects With Important Changes in Their Cardiac Repolarization Parameters for the Procurement of Skin and Blood Samples (iQTEST)

Selections of Subjects With Dramatic Changes in Their Cardiac Repolarization Parameters After a Pharmacologic Stimulus Aiming to Collect Their Skin Biopsy and Blood Cells

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.

Study Overview

• Status: Completed
• Conditions: Cardiology: RR / QT
• Intervention / Treatment: Drug: Erythromycin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rueil Malmaison, France, 92500
    • Biotrial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 4mg/Kg, IV during 20 min once
Experimental: Erythromycin	Drug: Erythromycin; 4mg/Kg, IV during 20 min once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolongation of cardiac QT due to erythromycin compare to Placebo reported as Delta QTcf	Delta QTcf is measured at H0, H0+20 minutes, and H0+1h20, on groups' erythromycin and placebo. QTcf may be adjusted based on the pharmacokinetic data to ensure time of the plasmatic pick is used.	1hour and 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison Delta QTcf eryhtromycin-sotalol	compare the effect of erythromycin and sotalol on QT prologation	over 3 hours
Assess the effect of erythromycin Twave morphologie changes	Analysis of Qwave morphologic changes	1hour and 20 min

Collaborators and Investigators

• Sponsor: Ectycell SASU
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Pierre and Marie Curie University
• Investigators: Study Director: Jean Sebastien Hulot, MD, University PMCurrie-INSERM

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 18, 2011
• First Posted (Estimate): April 19, 2011

Study Record Updates

• Last Update Posted (Estimate): September 15, 2011
• Last Update Submitted That Met QC Criteria: September 14, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Drug induced QT prolongation
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate
• Other Study ID Numbers: 2010-022000-41