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
  Purpose

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.


Condition Intervention Phase
Long QT Syndrome
Drug: Placebo
Drug: Ranolazine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Ranolazine in LQT3 Patients

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ranolazine
Ranolazine 1000 mg bid
Drug: Ranolazine
Patients will receive ranolazine 1000mg bid or matching placebo
Other Name: Raznexa
Placebo Comparator: Placebo
Matching Placebo
Drug: Placebo
Matching Placebo will be given
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01648205

Contacts
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

Locations
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
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   
Sub-Investigator: Spencer Z Rosero, MD         
Sponsors and Collaborators
University of Rochester
Gilead Sciences
Investigators
Principal Investigator: Wojciech Zareba, MD,PhD University of Rochester
  More Information

Publications:
Responsible Party: Wojciech Zareba, Professor of Medicine, University of Rochester
ClinicalTrials.gov Identifier: NCT01648205     History of Changes
Other Study ID Numbers: IN-US-259-0128
Study First Received: July 18, 2012
Last Updated: December 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
ranolazine
clinical trial

Additional relevant MeSH terms:
Long QT Syndrome
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities
Pathologic Processes
Ranolazine
Sodium Channel Blockers
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Membrane Transport Modulators
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014