The HOLIDAY (HOw ALcohol InDuces Atrial TachYarrhythmias) Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. |
Drug: Placebo
The placebo with be 0.45% saline solution ("half normal saline").
Other Names:
|
| Active Comparator: Ethanol Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. |
Drug: Ethanol
6% volume/volume ethanol in 0.45% saline solution.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Atrial Fibrillation Induction [This will be measured after study drug (ethanol or placebo) infusion. The measurement will be performed within 1 hour of the infusion.]
Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome.
Secondary Outcome Measures
- Change in Conduction Time [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.]
The atrial conduction time will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in Conduction Time
- Change in Atrial Effective Refractory Period (AERP) [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.]
The AERP will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in AERP
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94143 |
Sponsors and Collaborators
- University of California, San Francisco
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
- Principal Investigator: Gregory M Marcus, MD, MAS, University of California, San Francisco
- Principal Investigator: Jonathan W Dukes, MD, University of California, San Francisco
Study Documents (Full-Text)
More Information
Publications
None provided.- 12-08579
- 1R01AA022222-01
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Ethanol |
|---|---|---|
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. |
| Period Title: Overall Study | ||
| STARTED | 50 | 50 |
| COMPLETED | 50 | 50 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | Ethanol | Total |
|---|---|---|---|
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. | Total of all reporting groups |
| Overall Participants | 50 | 50 | 100 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
28
56%
|
34
68%
|
62
62%
|
| >=65 years |
22
44%
|
16
32%
|
38
38%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
61.14
(13.08)
|
58.78
(11.27)
|
60.51
(10.54)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
12
24%
|
14
28%
|
26
26%
|
| Male |
38
76%
|
36
72%
|
74
74%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
1
2%
|
1
1%
|
| Not Hispanic or Latino |
50
100%
|
48
96%
|
98
98%
|
| Unknown or Not Reported |
0
0%
|
1
2%
|
1
1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
8%
|
3
6%
|
7
7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
2%
|
2
4%
|
3
3%
|
| White |
45
90%
|
44
88%
|
89
89%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
2%
|
1
1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
50
100%
|
50
100%
|
100
100%
|
Outcome Measures
| Title | Number of Participants With Atrial Fibrillation Induction |
|---|---|
| Description | Induction of Atrial fibrillation will be attempted by pacing and isoproterenol infusion following study drug infusion. The ability to induce atrial fibrillation (yes or no) will be recorded as the primary outcome. |
| Time Frame | This will be measured after study drug (ethanol or placebo) infusion. The measurement will be performed within 1 hour of the infusion. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Ethanol |
|---|---|---|
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. |
| Measure Participants | 50 | 50 |
| Count of Participants [Participants] |
22
44%
|
24
48%
|
| Title | Change in Conduction Time |
|---|---|
| Description | The atrial conduction time will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in Conduction Time |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Ethanol |
|---|---|---|
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. |
| Measure Participants | 50 | 50 |
| Paroximal coronary sinus (CSp) to high right atrium (hRA) |
0.67
|
0.33
|
| CSp to Left upper pulmonary vein (LUPV) |
3.50
|
2.88
|
| Distal coronary sinus (CSd) to CSp |
0
|
0.33
|
| hRA to His bundle (His) |
-0.50
|
-2.00
|
| hRA to low right atrium (lRA) |
0.50
|
0.50
|
| LUPV to right upper pulmonary vein (RUPV) |
3.67
|
3.33
|
| RUPV to CSd |
1
|
2.33
|
| RUPV to His |
0.33
|
4.33
|
| Title | Change in Atrial Effective Refractory Period (AERP) |
|---|---|
| Description | The AERP will be measured before and after study drug infusion, and the difference between the two times will be recorded as the Change in AERP |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Ethanol |
|---|---|---|
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. |
| Measure Participants | 50 | 50 |
| Mean (95% Confidence Interval) [ms] |
1.59
|
-3.35
|
Adverse Events
| Time Frame | 1 year post-ablation | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Placebo | Ethanol | ||
| Arm/Group Description | The placebo will be administered to participants after the baseline electrophysiologic measurements are recorded. Placebo: The placebo with be 0.45% saline solution ("half normal saline"). | Ethanol (alcohol) will be administered to participants after the baseline electrophysiologic measurements are recorded. Ethanol: 6% volume/volume ethanol in 0.45% saline solution. | ||
All Cause Mortality |
||||
| Placebo | Ethanol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/50 (0%) | 0/50 (0%) | ||
Serious Adverse Events |
||||
| Placebo | Ethanol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/50 (0%) | 1/50 (2%) | ||
| Injury, poisoning and procedural complications | ||||
| Tamponade | 0/50 (0%) | 1/50 (2%) | 1 | |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Ethanol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/50 (2%) | 0/50 (0%) | ||
| General disorders | ||||
| Hypotension | 1/50 (2%) | 1 | 0/50 (0%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Gregory Marcus |
|---|---|
| Organization | University of California, San Francisco |
| Phone | (415) 353-2554 |
| Greg.Marcus@ucsf.edu |
- 12-08579
- 1R01AA022222-01