Alcohol Use, Unspecified
Conditions
Keywords
estradiol, reward, menstrual, hormone
Brief summary
This study will provide the first rigorous integrative test of the hypothesis that rapid rises in estradiol (a female hormone) increase the rewarding and disinhibiting effects of alcohol and that such increased sensitivity correlates with increased alcohol use. Identification of the behavioral mechanisms by which estradiol surges can increase alcohol use would provide a critical advancement of neurobiological theory of alcohol abuse in women, an understudied area, as well as provide new directions for personalization of alcohol abuse treatment in women. In this study, naturally-cycling women will be examined daily over their menstrual cycle using an integrative combination of daily ecological assessments of hormone fluctuations and alcohol use along with strategically-timed laboratory tests of their acute sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol.
Detailed description
A longitudinal study design will test hormonal influences across the menstrual cycle on women's naturalistic drinking behavior, as well as their acute sensitivity to the rewarding and disinhibiting effects of alcohol in the laboratory, two key mechanisms of its abuse potential. Subjects will attend a diagnostic visit to assess baseline clinical characteristics. In addition, subjects will attend two laboratory visits to test alcohol sensitivity at two key points in the cycle: during the early follicular phase when E2 is low and the late follicular phase when E2 is rising (see Figure 6). Every day after their first laboratory visit for 35 consecutive days, women will provide saliva samples each morning to assess hormonal levels and complete a self-report on their drinking behavior and alcohol craving every evening through a secure online server. The daily saliva and self-report data will allow fine-grained investigation of the lagged correlations between E2 and daily alcohol use patterns and alcohol craving across the menstrual cycle. The two laboratory visits will test and compare the acute sensitivity to rewarding and disinhibiting effects of a controlled dose of alcohol during the early follicular phase when E2 is low and the late follicular phase when E2 is rising. Volunteers will be followed daily to assess when they start their next menstrual cycle (i.e., the day they start bleeding). Within 1-2 days of that point, volunteers are scheduled to attend their initial diagnostic visit. Participants are then counterbalanced to begin the study during either their early follicular phase (approximately day 5) or their late follicular phase (approximately day 12) which is also when they begin their 35 days of consecutive daily data collection. This serves to counterbalance the order of the two alcohol sensitivity test sessions: early follicular versus late follicular phase. Ovulation testing and daily salivary E2 will confirm the proximity of the late follicular phase to ovulation, with the goal of ovulation occurring 1-3 days after the late follicular visit, and capturing a higher, rising E2 level in the late follicular phase relative to a lower level in the early follicular phase.
Interventions
DRUGPlacebo
Participants will attend two identical laboratory sessions to test sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol, once during the early follicular phase and once during the late follicular phase. The test battery consists of measures of rewarding effects and alcohol (or placebo) effects on disinhibition and impulsive choice. The placebo consists of 300 ml of lemon-flavored soda with a small amount (3 ml) of alcohol floated on top.
DRUGAlcohol
Participants will attend two identical laboratory sessions to test sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol, once during the early follicular phase and once during the late follicular phase. The test battery consists of measures of rewarding effects and alcohol effects on disinhibition and impulsive choice. The alcohol dose consists of 0.60 g/kg absolute alcohol that produces a peak blood-alcohol concentration of 80 mg/dl. Doses will be mixed with a carbonated, non-caffeinated, lemon-flavored soda and consumed within 10 minutes.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Mark Fillmore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* female * regular menstrual cycle * consume alcohol at least once per week * no history of drug or alcohol dependence
Exclusion criteria
* use of hormone-based medications * irregular menstrual cycle * current pregnancy * primary sensorimotor handicap * frank neurological disorder * pervasive developmental disorder * frank psychosis * diagnosed intellectual disability * medical condition contraindicating alcohol use * substance abuse history (except nicotine) * body mass index (BMI) 30 or above * alcohol abstainer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attentional Bias (Early Follicular Phase) | 1 day | Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image. |
| Attentional Bias (Late Follicular Phase) | 1 day | Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image. |
| Disinhibition (Early Follicular Phase) | 1 day | Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target). |
| Disinhibition (Late Follicular Phase) | 1 day | Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target). |
| Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase) | 1 day | a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding |
| Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase) | 1 day | a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding |
Countries
United States
Participant flow
Pre-assignment details
For this study participants are randomly started in Late Follicular Phase (Day 12) or Early Follicular Phase (Day 5) based on when they are enrolled in the study and which day of their menstrual cycle they are on when enrolled. This order does not affect the treatment given to each participant in any way. Every participant is given a placebo, then alcohol.
Participants by arm
| Arm | Count |
|---|---|
| Study Participants Participants in this group will track their menstrual cycle, provide daily saliva samples, and undergo two rounds of alcohol sensitivity testing (with both placebo and alcohol). | 100 |
| Total | 100 |
Baseline characteristics
| Characteristic | Study Participants |
|---|---|
| Age, Continuous | 23.98 years STANDARD_DEVIATION 3.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Region of Enrollment United States | 100 Participants |
| Sex: Female, Male Female | 100 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 0 / 100 |
| serious Total, serious adverse events | 0 / 100 |
Outcome results
Primary
Attentional Bias (Early Follicular Phase)
Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image.
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Attentional Bias (Early Follicular Phase) | Alcohol | 347.99 milliseconds | Standard Deviation 51.61 |
| Study Participants | Attentional Bias (Early Follicular Phase) | Placebo | 355.02 milliseconds | Standard Deviation 56.02 |
Primary
Attentional Bias (Late Follicular Phase)
Attentional bias is measured by the visual dot-probe task and provides an implicit assessment of the rewarding properties of alcohol as indicated by the degree to which an acute dose of alcohol increases the drinker's attention to alcohol cues is measured. Subjects look at images on a screen and their attention to various images is measured. An alcohol-related image and a neutral control image are presented briefly side-by-side, on a computer screen. An eye tracker embedded into the monitor provides an unobtrusive measure of the duration (dwell time) that volunteers look at each image.
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Attentional Bias (Late Follicular Phase) | Alcohol | 356.01 milliseconds | Standard Deviation 57.58 |
| Study Participants | Attentional Bias (Late Follicular Phase) | Placebo | 352.81 milliseconds | Standard Deviation 57.14 |
Primary
Disinhibition (Early Follicular Phase)
Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target).
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Disinhibition (Early Follicular Phase) | Alcohol | 0.107 proportion of inhibition failures | Standard Deviation 0.12 |
| Study Participants | Disinhibition (Early Follicular Phase) | Placebo | 0.04 proportion of inhibition failures | Standard Deviation 0.06 |
Primary
Disinhibition (Late Follicular Phase)
Disinhibition wil be measured by the cued go/no-go task, which requires participants to respond quickly to go targets and inhibit responses to no-go targets. Participants complete 250 trials in which they are presented with a cue, followed by a target. A go target is green, and participants are instructed to press a button when presented with a go target. A no-go target is blue, and participants are instructed to do nothing when this appears. A go cue predicts a go target with 80% accuracy, whereas a no-go cue predicts a no-go target with 80% accuracy. The condition of interest is when a go cue is followed by a no-go target. The proportion reported is the proportion of trials under this condition in which participants press the button (expecting a go target but presented with a no-go target).
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Disinhibition (Late Follicular Phase) | Alcohol | 0.134 proportion of inhibition failures | Standard Deviation 0.13 |
| Study Participants | Disinhibition (Late Follicular Phase) | Placebo | 0.045 proportion of inhibition failures | Standard Deviation 0.06 |
Primary
Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase)
a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase) | Alcohol | 56.99 score on a scale | Standard Deviation 25.61 |
| Study Participants | Subjective Ratings of the Rewarding Effects of Alcohol (Early Follicular Phase) | Placebo | 39.2 score on a scale | Standard Deviation 23.26 |
Primary
Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase)
a visual analog scale from 0-100, with 0 being not rewarding at all and 100 being very rewarding
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Participants | Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase) | Alcohol | 60.17 score on a scale | Standard Deviation 22.23 |
| Study Participants | Subjective Ratings of the Rewarding Effects of Alcohol (Late Follicular Phase) | Placebo | 39.43 score on a scale | Standard Deviation 22.37 |