Efficacy Study of Sodium Channel Blocker in LQT3 Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Rochester
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Wojciech Zareba, University of Rochester
ClinicalTrials.gov Identifier:
NCT01648205
First received: July 18, 2012
Last updated: December 11, 2013
Last verified: December 2013

July 18, 2012
December 11, 2013
September 2012
September 2014   (final data collection date for primary outcome measure)
QTc duration [ Time Frame: At 2 and 6 months after baseline ] [ Designated as safety issue: No ]
Change from baseline in QTc at 2 months and at 6 months
Same as current
Complete list of historical versions of study NCT01648205 on ClinicalTrials.gov Archive Site
Change in Novel ECG, Echo, and Holter-derived markers from baseline at 2 and 6 months [ Time Frame: At 2 months and 6 months ] [ Designated as safety issue: No ]
The investigators will evaluate the effects of ranolazine on novel ECG, echo and Holter-derived markers to determine whether they could be even more sensitive regarding effects of drug on repolarization and its dynamics, measuring changes from baseline at 2 months and at 6 months.
Novel ECG, Echo, and Holter-derived markers [ Time Frame: At 2 months and 6 months ] [ Designated as safety issue: No ]
The investigators will evaluate the effects of ranolazine on novel ECG, echo and Holter-derived markers to determine whether they could be even more sensitive regarding effects of drug on repolarization and its dynamics, measuring changes from baseline at 2 months and at 6 months.
Not Provided
Not Provided
 
Efficacy Study of Sodium Channel Blocker in LQT3 Patients
Ranolazine in LQT3 Patients

The purpose of this study is to determine whether late sodium channel blockade might be effective in shortening the QTc interval in various LQT3 mutations and be considered as a safe therapeutic option for LQT3 patients.

LQT3 mutations in the LQTS Registry will be studied using in vitro expression studies to determine whether ranolazine causes a decrease in late sodium current, slower recovery from inactivation and/or changes in time course of inactivation, ameliorating the causative functional effect of each individual mutation.

Individuals with select LQT3 mutations already studied in vitro will be invited to participate in a short term (2 day) study in the Clinical Research Center studying the effects of an oral dose of ranolazine on QTc duration and other ECG, echocardiogram and Holter-derived parameters.

The same individuals, as well as other individuals with the same mutation, will be invited to participate in a 6-month study involving ranolazine and matched placebo, to help evaluate the long-term effectiveness of ranolazine in the population. Periodic ECGs and 24-hour Holter recordings will be obtained for evaluation of QTc duration and other ECG and Holter-derived parameters.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Long QT Syndrome
  • Drug: Placebo
    Matching Placebo will be given
    Other Name: Placebo
  • Drug: Ranolazine
    Patients will receive ranolazine 1000mg bid or matching placebo
    Other Name: Raznexa
  • Active Comparator: Ranolazine
    Ranolazine 1000 mg bid
    Intervention: Drug: Ranolazine
  • Placebo Comparator: Placebo
    Matching Placebo
    Intervention: Drug: Placebo
Moss AJ, Zareba W, Schwarz KQ, Rosero S, McNitt S, Robinson JL. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008 Dec;19(12):1289-93. Epub 2008 Jul 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
September 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Genotyped positive for LQT3 (SCN5A) mutation
  • Age 21 years or older
  • Not currently taking an antiarrhythmic drug (beta blockers are allowed)
  • Enrolled in LQTS Registry

Exclusion Criteria:

  • Age less than 21 years
  • Not confirmed to have an LQT3 mutation
  • Significant co-morbidity that would preclude subject's safe participation in this study
  • Females who are pregnant or nursing
  • Females of childbearing age who are not using acceptable method of birth control
  • Evidence of prior sensitivity to ranolazine
  • Hepatic or renal disease that might adversely affect ranolazine excretion
  • Currently taking strong CYP3A inhibitors
  • Currently taking P-gp inhibitors
  • Currently taking CYP3A inducers
  • In vitro studies of specific mutation show no effect of ranolazine on late sodium current kinetics or show repolarization prolongation
Both
21 Years and older
No
Contact: Jennifer L Robinson, MS 585-275-8819 Jennifer.Robinson@heart.rochester.edu
Contact: Kristina J Cutter, MS 585-275-8825 Kris.Cutter@heart.rochester.edu
United States
 
NCT01648205
IN-US-259-0128
Yes
Wojciech Zareba, University of Rochester
University of Rochester
Gilead Sciences
Principal Investigator: Wojciech Zareba, MD,PhD University of Rochester
University of Rochester
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP