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

• ClinicalTrials.gov Identifier: NCT01338441
• Recruitment Status: Completed
• First Posted: April 19, 2011
• Last Update Posted: September 15, 2011
• Sponsor: Ectycell SASU
• Collaborators: Pierre and Marie Curie University; Institut National de la Santé Et de la Recherche Médicale, France
• Information provided by (Responsible Party): Ectycell SASU

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cardiology: RR / QT	Drug: Erythromycin; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• 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 Start Date: March 2011
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Prolongation of cardiac QT due to erythromycin compare to Placebo reported as Delta QTcf [ Time Frame: 1hour and 20 minutes ]
   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.

Secondary Outcome Measures :

1. Comparison Delta QTcf eryhtromycin-sotalol [ Time Frame: over 3 hours ]
   compare the effect of erythromycin and sotalol on QT prologation
2. Assess the effect of erythromycin Twave morphologie changes [ Time Frame: 1hour and 20 min ]
   Analysis of Qwave morphologic changes

Eligibility Criteria

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

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

Contacts and Locations

Locations

France

BIOTRIAL

Rueil Malmaison, France, 92500

Sponsors and Collaborators

Ectycell SASU

Pierre and Marie Curie University

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

• Study Director: Jean Sebastien Hulot, MD; University PMCurrie-INSERM

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. pii: e19406. doi: 10.7554/eLife.19406.

• Responsible Party: Ectycell SASU
• ClinicalTrials.gov Identifier: NCT01338441 History of Changes
• Other Study ID Numbers: 2010-022000-41
• First Posted: April 19, 2011
• Last Update Posted: September 15, 2011
• Last Verified: September 2011

Keywords provided by Ectycell SASU:

Drug induced QT prolongation

Additional relevant MeSH terms:

Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action