Oxytocin Effects on Cardiac Electrophysiology

NCT01780337 | Completed Early Phase 1 Results DMC

• 1 other identifier: AAAC7383
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiac Arrhythmia

Keywords

Oxytocin; Arrhythmia

Outcome Measures

Primary Outcomes (3)

• Change in Electrophysiology Measure of AH Interval

  First measured at time zero, then at 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.

  Baseline and 30 min

• Change in Electrophysiology Measure of HV Interval

  First measured at time zero, then at 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.

  Baseline and 30 min

• Change in Electrophysiology Measure of Right Ventricular Refractory Period

  First measured at time zero, then at 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.

  Baseline and 30 min

Study Arms (2)

Oxytocin

ACTIVE COMPARATOR

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

Saline

PLACEBO COMPARATOR

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

Interventions

Oxytocin DRUG

Intranasal dose of 20 IU oxytocin

Also known as: Pitocin

Oxytocin

Saline OTHER

Intranasal dose of saline

Saline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• William Whang: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (15)

• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3;125(1):e2-e220. doi: 10.1161/CIR.0b013e31823ac046. Epub 2011 Dec 15. No abstract available.

  PMID: 22179539 BACKGROUND

• Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001 Oct 30;104(18):2158-63. doi: 10.1161/hc4301.098254.

  PMID: 11684624 BACKGROUND

• Josephson M, Wellens HJ. Implantable defibrillators and sudden cardiac death. Circulation. 2004 Jun 8;109(22):2685-91. doi: 10.1161/01.CIR.0000129322.97266.F3. No abstract available.

  PMID: 15184292 BACKGROUND

• Irvine J, Basinski A, Baker B, Jandciu S, Paquette M, Cairns J, Connolly S, Roberts R, Gent M, Dorian P. Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue. Psychosom Med. 1999 Nov-Dec;61(6):729-37. doi: 10.1097/00006842-199911000-00001.

  PMID: 10593621 BACKGROUND

• Whang W, Kubzansky LD, Kawachi I, Rexrode KM, Kroenke CH, Glynn RJ, Garan H, Albert CM. Depression and risk of sudden cardiac death and coronary heart disease in women: results from the Nurses' Health Study. J Am Coll Cardiol. 2009 Mar 17;53(11):950-8. doi: 10.1016/j.jacc.2008.10.060.

  PMID: 19281925 BACKGROUND

• Empana JP, Jouven X, Lemaitre RN, Sotoodehnia N, Rea T, Raghunathan TE, Simon G, Siscovick DS. Clinical depression and risk of out-of-hospital cardiac arrest. Arch Intern Med. 2006 Jan 23;166(2):195-200. doi: 10.1001/archinte.166.2.195.

  PMID: 16432088 BACKGROUND

• Whang W, Albert CM, Sears SF Jr, Lampert R, Conti JB, Wang PJ, Singh JP, Ruskin JN, Muller JE, Mittleman MA; TOVA Study Investigators. Depression as a predictor for appropriate shocks among patients with implantable cardioverter-defibrillators: results from the Triggers of Ventricular Arrhythmias (TOVA) study. J Am Coll Cardiol. 2005 Apr 5;45(7):1090-5. doi: 10.1016/j.jacc.2004.12.053.

  PMID: 15808769 BACKGROUND

• Carney RM, Blumenthal JA, Freedland KE, Stein PK, Howells WB, Berkman LF, Watkins LL, Czajkowski SM, Hayano J, Domitrovich PP, Jaffe AS. Low heart rate variability and the effect of depression on post-myocardial infarction mortality. Arch Intern Med. 2005 Jul 11;165(13):1486-91. doi: 10.1001/archinte.165.13.1486.

  PMID: 16009863 BACKGROUND

• Carney RM, Blumenthal JA, Stein PK, Watkins L, Catellier D, Berkman LF, Czajkowski SM, O'Connor C, Stone PH, Freedland KE. Depression, heart rate variability, and acute myocardial infarction. Circulation. 2001 Oct 23;104(17):2024-8. doi: 10.1161/hc4201.097834.

  PMID: 11673340 BACKGROUND

• Grippo AJ, Trahanas DM, Zimmerman RR 2nd, Porges SW, Carter CS. Oxytocin protects against negative behavioral and autonomic consequences of long-term social isolation. Psychoneuroendocrinology. 2009 Nov;34(10):1542-53. doi: 10.1016/j.psyneuen.2009.05.017. Epub 2009 Jun 23.

  PMID: 19553027 BACKGROUND

• Norman GJ, Cacioppo JT, Morris JS, Malarkey WB, Berntson GG, Devries AC. Oxytocin increases autonomic cardiac control: moderation by loneliness. Biol Psychol. 2011 Mar;86(3):174-80. doi: 10.1016/j.biopsycho.2010.11.006. Epub 2010 Nov 30.

  PMID: 21126557 BACKGROUND

• COVINO BG. CARDIAC EFFECTS OF SYNTHETIC OXYTOCIN (SYNTOCINON). Am Heart J. 1963 Nov;66:627-31. doi: 10.1016/0002-8703(63)90317-x. No abstract available.

  PMID: 14083782 BACKGROUND

• Charbit B, Mercier FJ, Benhamou D. Modification of Tp-e and QTc intervals during caesarean section under spinal anaesthesia. Anaesthesia. 2010 Sep;65(9):956-7. doi: 10.1111/j.1365-2044.2010.06466.x. No abstract available.

  PMID: 21198494 BACKGROUND

• Liou SC, Chen C, Wong SY, Wong KM. Ventricular tachycardia after oxytocin injection in patients with prolonged Q-T interval syndrome--report of two cases. Acta Anaesthesiol Sin. 1998 Mar;36(1):49-52.

  PMID: 9807850 BACKGROUND

• MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011 Sep;36(8):1114-26. doi: 10.1016/j.psyneuen.2011.02.015. Epub 2011 Mar 23.

  PMID: 21429671 BACKGROUND

MeSH Terms

Conditions

Arrhythmias, Cardiac

Interventions

Oxytocin; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: William Whang
• Organization: Columbia University

ww42@cumc.columbia.edu

212-305-8620

Study Officials

• William Whang, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine at CUMC

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: January 31, 2013
• Study Start: January 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: July 21, 2016
• Results First Posted: June 17, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)