Certain People With Atrial Fibrillation May Have Changes on Ecg When Given Procainamide That May be Related to a Genetic Difference

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Dawood Darbar, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01205529
First received: September 17, 2010
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to look for a similarity in people's genes that may help understand which people could benefit from certain drugs for the treatment of atrial fibrillation.


Condition Intervention
Atrial Fibrillation
Drug: Procainamide

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Prospective Evaluation of a Potential Sodium Channel-Related Endophenotype

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • ST segment elevation ≥ 1 mm in the right precordial leads (V1-V3), either at baseline or manifested after Na+ channel block with intravenous procainamide [ Time Frame: During (5, 10, 15, 20, 25, 30 minutes after initiating) or up to 15 minutes after completion of intravenous procainamide infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 750
Study Start Date: November 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Atrial Fibrillation with ST changes on electrocardiogram
Those patients with ST segment or J Point elevation on electrocardiogram. Can be on initial screening electrocardiogram or on electrocardiograms during procainamide infusion. These subjects will also have SCN5A mutation.
Drug: Procainamide
One time intravenous infusion of Procainamide administered over 30 minutes. Dosage is calculated as 10mg/kg based on subject's ideal body weight.

Detailed Description:

Current drug therapies to suppress AF are incompletely and unpredictably effective and carry significant (albeit generally small) risks of serious adverse effects, including drug-induced long QT syndrome (diLQTS), other forms of proarrhythmia, increased mortality through uncertain mechanisms, and extracardiac toxicity. Identification of clinical and genetic subtypes of AF will permit stratification of therapeutic approaches and thereby facilitate the practice of personalized medicine. Furthermore, limited success of drug therapy and increase in drug toxicity in AF is probably because the arrhythmia represents a final common pathway of multiple initiating mechanisms, including those some that are genetically-defined.

Identifying specific intermediate phenotypes ("endophenotypes") associated with defined clinical courses in AF represents a potential method to systematically subtype patients by underlying mechanism and represents a much-needed clinical advance. Clinical endophenotypes that have been studied include atrial fibrillatory rate, prolonged signal-averaged P-wave duration, and biomarker profiles. The endophenotype we will study here is right precordial ST segment elevation, seen not only in Brugada syndrome (BrS) (where it is unmasked by sodium channel blocking drugs) but also commonly in lone AF and in patients with AF-associated rare variants in genes encoding the cardiac sodium channel α- or β-subunits. Taken together these data suggest the hypothesis to be tested in this study, that variants in multiple genes can culminate in a similar AF-prone substrate by reducing sodium current that can be identified by screening for baseline or manifest right precordial ST segment elevation endophenotype after sodium channel block with intravenous procainamide.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Undergoing AF ablation at Vanderbilt or MGH

Exclusion Criteria:

  • Patients taking membrane active anti-arrhythmic drugs with sodium channel blocking properties (amiodarone, dronedarone, flecainide, propafenone) at the time of the ablation
  • Patients with a history of Brugada syndrome or type 1 Brugada ECG pattern on the baseline ECG
  • Patients with a history of drug-induced torsades de pointes
  • Patients with a known history of hypersensitivity to procainamide, procaine or related drugs
  • Patients with a history of systemic lupus erythematosus and myasthenia gravis
  • Patients with a history of second degree AV block (Mobitz type II) or third degree AV block
  • Women of child-bearing potential unless post-menopausal, surgically sterile, or have a negative pregnancy test day on the day of procedure
  • Patients with dual chamber pacemakers or implantable defibrillators requiring ventricular pacing (uninterpretable ECG)
  • Patients unable to give informed consent
  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: NCT01205529

Contacts
Contact: Gayle Kucera, RN 615-936-6069 gayle.a.kucera@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Gayle Kucera, RN    615-936-6069    gayle.a.kucera@vanderbilt.edu   
Contact: Kris Norris, RN    615-936-1131    kris.norris@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Dawood Darbar, MD, PhD Vanderbilt University
  More Information

No publications provided

Responsible Party: Dawood Darbar, Associate Professor of Medicine and Pharmacology, Director of Arrhythmia Services, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01205529     History of Changes
Other Study ID Numbers: IRB # 100800, U19HL065962
Study First Received: September 17, 2010
Last Updated: December 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Atrial Fibrillation
ST elevation
Genotype

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Procainamide
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014