Binge Drinking
Conditions
Brief summary
This study evaluates the impact of evening alcohol consumption on sympathetic activity and baroreflex function in binge drinkers. Our central hypothesis is that evening binge alcohol consumption will lead to sympathetic overactivity and blunted baroreflex function.
Detailed description
This study will recruit male and female binge drinkers who will participate in a randomized, cross-over, double-blind, placebo-based study to examine the impact of an evening of alcohol vs. placebo/fluid-control on autonomic and cardiovascular control at night and the subsequent morning. The study will utilize established techniques for assessing sleep (polysomnography) and autonomic/cardiovascular control (microneurography, beat-to-beat finger plethysmography, electrocardiogram, etc.). All subjects will undergo a familiarization night in the sleep laboratory prior to their first randomized test session with either alcohol or placebo/fluid-control. Both men and women will be tested to address a secondary aim of determining the impact of sex (male vs. female) and ovarian cycle (early follicular vs. midluteal phase) on sympathetic neural responsiveness to evening alcohol in binge drinkers. Finally, as a tertiary/exploratory aim, participants that have a respiratory disturbance index of ≥5 episodes per hour during the alcohol treatment will be asked to consider one additional overnight session where they will be randomly assigned to either continuous positive airway pressure (CPAP) or sham-CPAP for one additional night of evening alcohol consumption.
Interventions
OTHERAlcohol vs. Placebo
Using a randomized, cross-over design, all subjects will consume evening alcohol (and a fluid-control placebo) in a dose that mimics binge drinking.
Sponsors
University of Chicago
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Baylor University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women age 21 - 40 years * Binge drinkers as defined by a pattern of consuming ≥4 drinks if female (≥5 drinks if males) in ≤ 2 hours on more than one occasion within the past 6 months, and at least once in the past 30 days. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) definition of a drink will be used. * Women must be eumenorrheic and premenopausal with regular and consistent menstrual cycles (i.e., \ 25-30 days ovarian/uterine cycles that include 2-7 days of menstruation) * Willingness to abstain from exercise and caffeine at least 12 hours prior to any autonomic and cardiovascular testing, and abstain from alcohol 24 hours prior to any autonomic and cardiovascular testing (unless experimentally administered).
Exclusion criteria
* Body mass index ≥ 35 kg/m2 * Smokers * A physician diagnosis of diabetes * Pregnancy * Taking any cardiovascular medications * Severe obstructive sleep apnea as determined by an apnea-hypopnea index of ≥ 30 episodes per hour * Moderate-to-severe Alcohol Use Disorder (AUD) as determined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) * Individuals suspected to have mutant alcohol dehydrogenase 2 (ALDH2) isoenzyme as determined using a validated flushing questionnaire * Women using hormonal contraceptives (i.e., oral, intrauterine, etc.) in the prior 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sympathetic Nerve Activity Burst Frequency | 1 month | Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode. |
| Sympathetic Nerve Activity Burst Incidence | 1 month | Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode. Burst incidence is calculated as the number of sympathetic bursts per 100 heartbeats. This measure takes into account varying heart rates on sympathetic activity by normalizing to each individual's heartbeat. Higher calculated number equates to higher sympathetic activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous Sympathetic Baroreflex Sensitivity | 1 month | The linear relationship between beat-to-beat blood pressure and sympathetic nerve activity expressed as bursts/100 heart beats. Sympathetic baroreflex sensitivity is determined using the slope of the weighted linear regression of diastolic blood pressure and MSNA burst incidence. Diastolic blood pressure values of individual cardiac cycles were binned into 3 mmHg intervals, and the MSNA burst incidence was determined and subsequently plotted against corresponding diastolic blood pressure bins. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Nocturnal Blood Pressure Dip | 1 month | Change in nocturnal blood pressure during sleep when compared to evening/morning wakefulness. |
| Sleep Quality | 1 month | Polysomnography will be used to determine the quality of sleep, with a primary focus on the apnea-hypopnea index. |
| Sympathetic Reactivity | 1 month | The change in muscle sympathetic nerve activity during an acute laboratory stressor. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited by word-of-mouth and advertisements. 169 participants were screened for eligibility.
Pre-assignment details
38/169 participants were randomized. Of the 131 that were not randomized 100 did not meet inclusion criteria or did not consent and 31 were lost to follow-up/drop out.
Participants by arm
| Arm | Count |
|---|---|
| Fluid Control, Then Alcohol Participants first received a fluid control drink (i.e., juice) of the same volume of fluid as the alcohol condition. After at least a one-month washout period, they then received the alcohol condition.
Alcohol vs. Placebo: Using a randomized, cross-over design, all subjects will consume evening alcohol (and a fluid-control placebo) in a dose that mimics binge drinking. | 16 |
| Alcohol, Then Fluid Control Participants first received the alcohol condition with 95% ethanol and fruit juice (1:3 ratio). After at least a one-month washout period, they then received the fluid control condition with a volume fluid match.
Alcohol vs. Placebo: Using a randomized, cross-over design, all subjects will consume evening alcohol (and a fluid-control placebo) in a dose that mimics binge drinking. | 22 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
Baseline characteristics
| Characteristic | Fluid Control, Then Alcohol | Alcohol, Then Fluid Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 22 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 19 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 13 Participants | 19 Participants | 32 Participants |
| Region of Enrollment United States | 16 participants | 22 participants | 38 participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 2 / 38 | 1 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
Sympathetic Nerve Activity Burst Frequency
Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode.
Time frame: 1 month
Population: 26 total participants were analyzed for primary outcome measures that completed both arms (fluid control vs. alcohol) of the study, using a randomized crossover design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluid Control | Sympathetic Nerve Activity Burst Frequency | 18 Burst/Min | Standard Deviation 9 |
| Alcohol | Sympathetic Nerve Activity Burst Frequency | 20 Burst/Min | Standard Deviation 8 |
Comparison: Statistical analysis on Burst Frequency (Burst/Min)p-value: 0.283t-test, 2 sided
Comparison: Statistical analysis on Burst Incidence (Burst/100hb)p-value: 0.92t-test, 2 sided
Primary
Sympathetic Nerve Activity Burst Incidence
Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode. Burst incidence is calculated as the number of sympathetic bursts per 100 heartbeats. This measure takes into account varying heart rates on sympathetic activity by normalizing to each individual's heartbeat. Higher calculated number equates to higher sympathetic activity.
Time frame: 1 month
Population: 26 total participants were analyzed for primary outcome measures that completed both arms (fluid control vs. alcohol) of the study, using a randomized crossover design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluid Control | Sympathetic Nerve Activity Burst Incidence | 31 burst/100 heart beats | Standard Deviation 16 |
| Alcohol | Sympathetic Nerve Activity Burst Incidence | 31 burst/100 heart beats | Standard Deviation 12 |
Secondary
Spontaneous Sympathetic Baroreflex Sensitivity
The linear relationship between beat-to-beat blood pressure and sympathetic nerve activity expressed as bursts/100 heart beats. Sympathetic baroreflex sensitivity is determined using the slope of the weighted linear regression of diastolic blood pressure and MSNA burst incidence. Diastolic blood pressure values of individual cardiac cycles were binned into 3 mmHg intervals, and the MSNA burst incidence was determined and subsequently plotted against corresponding diastolic blood pressure bins.
Time frame: 1 month
Population: 11 total participants were analyzed for the secondary outcome measure that completed both arms of the study (fluid control vs. alcohol), with a randomized crossover design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluid Control | Spontaneous Sympathetic Baroreflex Sensitivity | -2 MSNA Bursts/100 heart beats/mmHg | Standard Deviation 1 |
| Alcohol | Spontaneous Sympathetic Baroreflex Sensitivity | -2 MSNA Bursts/100 heart beats/mmHg | Standard Deviation 1 |
p-value: 0.888t-test, 2 sided
Other Pre-specified
Nocturnal Blood Pressure Dip
Change in nocturnal blood pressure during sleep when compared to evening/morning wakefulness.
Time frame: 1 month
Other Pre-specified
Sleep Quality
Polysomnography will be used to determine the quality of sleep, with a primary focus on the apnea-hypopnea index.
Time frame: 1 month
Other Pre-specified
Sympathetic Reactivity
The change in muscle sympathetic nerve activity during an acute laboratory stressor.
Time frame: 1 month