Oxytocin Effects on Cardiac Electrophysiology

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Columbia University
Sponsor:
Information provided by (Responsible Party):
William Whang, Columbia University
ClinicalTrials.gov Identifier:
NCT01780337
First received: January 29, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

In this pilot study the investigators will perform a double-blind randomized trial of intranasal oxytocin on measures of cardiac refractoriness, among individuals who are undergoing clinically indicated catheter ablation procedures for paroxysmal atrial fibrillation. The investigators seek to enroll 20 patients for this study, for the purpose of estimating effect sizes for a larger future study.


Condition Intervention Phase
Cardiac Arrhythmia
Drug: Oxytocin
Other: Saline
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Oxytocin Effects on Cardiac Electrophysiology

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Change in electrophysiology measure of AH interval [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: No ]
    First measured at time zero, then at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.

  • Change in electrophysiology measure of HV interval [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: No ]
    First measured at time zero, then at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.

  • Change in electrophysiology measure of atrial refractory period [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: No ]
    First measured at time zero, then at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.

  • Change in electrophysiology measure of right ventricular refractory period [ Time Frame: Baseline and 1 hour ] [ Designated as safety issue: No ]
    First measured at time zero, then at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, the investigators will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'pre- ablation' period normally takes 45 minutes to one hour.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Oxytocin
Patients will be administered an intranasal dose of the study drug, 20 IU oxytocin. Repeat electrophysiologic measurements will be assessed at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, we will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'preablation' period normally takes 45 minutes to one hour.
Drug: Oxytocin
Other Name: Intranasal dose of 20 IU oxytocin
Placebo Comparator: Saline
patients will be administered an intranasal dose of saline. Repeat electrophysiologic measurements will be assessed at 15 minutes and 30 minutes after administration of the study medication/placebo. During the waiting periods in between the electrophysiologic measurements, we will continue with the standard protocol for an AF ablation, including transseptal puncture and left atrial mapping, performed prior to initiation of general anesthesia and actual delivery of ablation lesions. This 'preablation' period normally takes 45 minutes to one hour.
Other: Saline
Other Name: Intranasal dose of saline

Detailed Description:

Despite widespread advances in the treatment of coronary artery disease and the growing use of automated external defibrillators and implantable cardioverter-defibrillators (ICDs) to treat ventricular arrhythmias, sudden cardiac death (SCD) due to ventricular arrhythmia remains a major public health problem. National estimates of SCD or out-of- hospital cardiac arrest range from 400,000 to 450,000 events annually. Although cardiac mortality rates have declined over time, the proportion of cardiac deaths that are sudden has increased during a time when major advances in device therapy for the prevention and treatment of SCD have taken place. This unfavorable trend is a consequence of the inability to accurately identify those who will die suddenly from a lethal ventricular arrhythmia and to disseminate effective preventive strategies for populations at risk.

Observational evidence has indicated that depression is associated with risk of SCD, both in patients with coronary artery disease as well as in individuals without heart disease. In patients with ICDs, depressive symptoms are associated with increased risk of shocks for ventricular arrhythmia, suggesting that ventricular arrhythmia is more common in depressed individuals. A leading candidate mechanism that may account for the association between depression and ventricular arrhythmia involves cardiac autonomic dysfunction; for instance, multiple studies have shown that depressed individuals have abnormal heart rate variability.

Recent evidence has emerged about the potential importance of oxytocin in the cardiovascular response to stress and depression. Oxytocin is a 9-amino acid peptide that is produced in the hypothalamus and released into the central nervous system and the bloodstream. Oxytocin has both hormone and neurotransmitter function, and affects targets including the hypothalamus, amygdala, hippocampus, brainstem, heart, uterus, and regions of the spinal cord that regulate the autonomic nervous system. Polymorphisms of the oxytocin receptor have been associated with improved cardiovascular responses to laboratory stress in humans.

Exogenous administration of intravenous oxytocin in a prairie vole model of isolation has been shown to protect against the heart rate response to social isolation and to improve heart rate variability. In addition, intranasal oxytocin administered to humans augments both sympathetic and parasympathetic modulation of the heart rate. Initial studies of intravenous oxytocin demonstrated direct effects on cardiac arrhythmias in animal models, even including termination of ventricular fibrillation, suggestive of a quinidine-like action on myocardial excitability. However, administration of intravenous oxytocin in women after delivery has been associated with abnormalities in cardiac repolarization and even with induced ventricular arrhythmia. Therefore, although there is reason to believe that administration of exogenous oxytocin may affect the probability of arrhythmia, the direction of this impact is unclear.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females older than 18 and younger than 85 years of age;
  • Undergoing catheter ablation for paroxysmal atrial fibrillation;
  • Presenting in sinus rhythm at the time of their procedure.

Exclusion Criteria:

  • Left ventricular ejection fraction <0.40;
  • Paced rhythm >50 percent of the time by device interrogation if a pacemaker is present.
  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: NCT01780337

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: James Peacock, MD       jp2341@columbia.edu   
Principal Investigator: William Whang, MD         
Sponsors and Collaborators
William Whang
Investigators
Principal Investigator: William Whang, MD Columbia University
  More Information

Publications:

Responsible Party: William Whang, Associate Professor of Medicine at CUMC, Columbia University
ClinicalTrials.gov Identifier: NCT01780337     History of Changes
Other Study ID Numbers: AAAC7383
Study First Received: January 29, 2013
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Oxytocin
Arrhythmia

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014