Clinical trial NCT01996943: The HOLIDAY (HOw ALcohol InDuces Atrial TachYarrhythmias) Study
Official title: Investigating the Effects of Ethanol on Atrial Fibrillation Susceptibility and Pathogenesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Alcohol
Keywords: Atrial Fibrillation
Alcohol
Electrophysiologic properties of the atria
Randomized Clinical Study
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2013-11-27
Enrollment: 100
Sex: ALL
Minimum age (years): 21
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Atrial fibrillation (AF) is the most common sustained arrhythmia in the United States and it has been associated with ethanol use. Understanding how ethanol affects the electrical properties of the heart and induces AF has important public health implications. The objective of this research is to investigate the mechanistic relationship between ethanol and atrial fibrillation in humans by performing a placebo controlled study looking at the electrical properties of the heart in patients receiving intravenous ethanol or placebo. The investigators hypothesize that ethanol increases the susceptibility of human myocardium to atrial fibrillation through electrophysiologic changes in the atrial myocardium in the acute setting.

Detailed description: The purpose of this study is to look for changes in the electrical properties of heart that may be caused by ethanol (commonly referred to as alcohol) and specifically how ethanol may trigger episodes of the most common abnormal heart rhythm, atrial fibrillation (AF). This study will demonstrate the mechanism of ethanol induced atrial fibrillation and clarify the health effects of one of the worlds' most popular drugs (ethanol). With this understanding, physicians may be able to better identify those patients most at risk for ethanol induced AF and target public health campaigns towards this vulnerable population.

Patients in this study will undergo an electrophysiologic study both prior to and after receiving either an ethanol or placebo infusion. This electrophysiology study will measure AF inducibility (the primary outcome), left and right atrial conduction times, and the atrial effective refractory period in multiple locations (AERP). The changes in the conduction times and AERPs (before and after study drug infusion) will be recorded as secondary outcomes.

About 100 people will participate in this study. 50 people will be randomized to receive intravenous ethanol, and 50 people will be randomized to receive an intravenous placebo. The placebo will be in the form of 0.45% saline solution ("half normal saline") and the alcohol will be in the form of 6% volume/volume ethanol in 0.45% saline solution.

Eligibility criteria: Inclusion Criteria:

* Patients aged 21-80 with paroxysmal atrial fibrillation (AF), supraventricular tachycardia, or undifferentiated palpitations who are to undergo either an elective ablation procedure (for AF, atrial flutter, atria tachycardia, atrial ventricular nodal reentrant tachycardia (AVNRT), or atrial ventricular reentrant tachycardia (AVRT)) or a diagnostic electrophysiology study in order to diagnose and treat their clinical arrhythmia at the University of California, San Francisco (UCSF) will be eligible for enrollment.

Exclusion criteria:

* Patients will be excluded if they are not in normal sinus rhythm (i.e. in AF, atrial tachycardia, atrial flutter, or incessant AVNRT/AVRT) at the time of onset of the procedure, any history of substance abuse or alcoholism as determined by history, AUDIT questionnaire, or chart review, left ventricular ejection fraction \<50%, inability to give informed consent, liver dysfunction (elevated aspartate aminotransferase , alanine aminotransferase, total bilirubin, or alkaline phosphatase \>2x normal), clinical evidence of liver disease (enlarged liver, caput medusa, spider angiomas, or other signs of liver disease on exam), or pregnancy.

Primary outcomes:
measure: Number of Participants With Atrial Fibrillation Induction
timeFrame: This will be measured after study drug (ethanol or placebo) infusion. The measurement will be performed within 1 hour of the infusion.
Secondary outcomes:
measure: Change in Conduction Time
timeFrame: This will be assessed during the experimental study from the Conduction Times that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion.
measure: Change in Atrial Effective Refractory Period (AERP)
timeFrame: This will be assessed during the experimental study from the AERPs that are measured before and after the study drug infusion. The measurements will be performed within 1 hour of the infusion.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Gregory M Marcus, MD, MAS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Jonathan W Dukes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marcus GM, Dukes JW, Vittinghoff E, Nah G, Badhwar N, Moss JD, Lee RJ, Lee BK, Tseng ZH, Walters TE, Vedantham V, Gladstone R, Fan S, Lee E, Fang C, Ogomori K, Hue T, Olgin JE, Scheinman MM, Hsia H, Ramchandani VA, Gerstenfeld EP. A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology. JACC Clin Electrophysiol. 2021 May;7(5):662-670. doi: 10.1016/j.jacep.2020.11.026. Epub 2021 Jan 27.