Alcohol Drinking, Alcohol Intoxication, Alcoholism
Conditions
Brief summary
Alcohol use disorder (AUD) impacts millions of Americans and is associated with significant behavioral, social, economic, medical, and neurobiological dysfunction, yet current behavioral treatments for AUD are only modestly effective. The proposed research will test the efficacy of a novel behavioral intervention, which combines brain stimulation with mindfulness-based relapse prevention, and is hypothesized to improve neural dysfunction and ultimately lead to large effect size reductions in heavy drinking among individuals with AUD. Given that mindfulness and brain stimulation are already available for home use there is great potential for the ultimate dissemination of the intervention on a large scale, which could have a significant impact on public health.
Detailed description
Heavy drinking (defined as 4+/5+ drinks per occasion for women/men) and alcohol use disorder (AUD) are a significant public health problem. Modestly effective pharmacological and psychosocial treatments for AUD exist, yet some heavy drinking (i.e., relapse) is the most common outcome following AUD treatment. Continued development of innovative and efficacious interventions that reduce heavy drinking and specifically target risk factors for heavy drinking is thus clearly warranted. One novel intervention that has considerable promise for reducing heavy drinking is mindfulness-based relapse prevention (MBRP). MBRP is a behavioral intervention for substance use disorder that was designed to target experiences of craving and other risk factors for heavy drinking. Based on the results of numerous studies, MBRP is feasible and efficacious in the treatment of AUD. However the effect sizes of MBRP remain small and many individuals struggle with engaging in the mindfulness practices early in treatment. There is preliminary evidence that combining a non-invasive form of brain stimulation, transcranial direct current stimulation (tDCS), may improve engagement with mindfulness practices and lead to significant reductions in heavy drinking following treatment. The goal of the proposed study is to examine the efficacy of a mindfulness + tDCS intervention in reducing heavy drinking and impacting hypothesized mechanisms of behavior change among individuals with AUD who are interested in reducing their heavy drinking. In the proposed study, a research team with complementary expertise in AUD treatment, mindfulness-based interventions, brain stimulation, and cognitive neuroscience will combine self-report, behavioral, and neurophysiological data collection via electroencephalography (EEG) to study the psychological and neurophysiological mechanisms of treatment efficacy following a novel, promising intervention that combines brain stimulation with mindfulness training. The mindfulness based intervention in combination with active tDCS is hypothesized to lead to significant reductions in drinks per drinking day after 8 weeks of treatment and these reductions will be maintained up to 2 months following treatment. Further, the effect of active tDCS on drinks per drinking day at the 2 month follow-up will be mediated by greater mindfulness, greater inhibitory control and reductions in craving and negative affect during treatment and at the post-treatment assessment. Approximately 86 individuals meeting criteria for AUD will be randomly assigned to 8 sessions of either MBRP combined with active tDCS (up to 2.0 milliamp current) or MBRP combined with a sham tDCS (no current) control condition. The proposed study will examine the efficacy (Primary Aim) and psychological and neurophysiological mechanisms of treatment efficacy using behavioral measures and EEG (Secondary Aim). In addition to addressing the question of whether adding active tDCS to MBRP enhances efficacy, it will further examine issues of neurophysiological and behavioral treatment mechanisms to better inform the design of a future large efficacy trial.
Interventions
DEVICEBrain stimulation with mindfulness-based relapse prevention
Participants will participate in weekly or twice weekly group mindfulness based relapse prevention (MBRP) + transcranial direct current stimulation (tDCS) intervention sessions for up to eight weeks. All participants will receive 8 two hour sessions of MBRP + tDCS, regardless of the group schedule. Subjects will receive 30 minutes of either active or sham tDCS stimulation, depending on their group assignment. After tDCS, sessions will include discussions of mindfulness as a means of coping with craving, cognitions, and emotions, role play exercises, and mindfulness practice.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of New Mexico
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. interested in reducing alcohol drinking 2. right-handed
Exclusion criteria
1. lifetime diagnosis of schizophrenia or bipolar disorder or current substance use disorder other than nicotine or marijuana 2. cardiac pacemaker 3. implantable defibrillator 4. metal objects in upper body that might interfere with tDCS, or that tDCS may interfere with their function, including metal plates, screws and prosthetics in head, certain older tattoos and permanent makeup using metal containing inks, aneurysm clips, neural stimulators of any kind, ear implants, insulin pumps, drug infusion devices and dental appliances 5. for females, pregnant or attempting to get pregnant 6. history of seizures or seizure disorder 7. allergic to latex, rubber, conductive medium like saline or electrode gel 8. if assigned to active tDCS and unable to tolerate 1.5 mA of tDCS during a baseline stimulation session
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Drinking Day | Post-treatment and 2-month follow-up | The Form 90 will be used to derive estimates of the primary outcome: drinks (standard drink=14 grams of pure alcohol) per drinking day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Heavy Drinking Days | Post-treatment and 2-month follow-up | The Form 90 will be used to derive estimates of the secondary outcome: percent heavy drinking days, where heavy drinking is defined as 4+ drinks per occasion for women and 5+ drinks per occasion for men. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cue Reactivity at the Post-Treatment Assessment | Post-treatment | To measure cue reactivity to alcohol, the investigators will use a visual cue presentation task. Participants will view pictures of alcohol containing beverages and neutral pictures from the International Affective Pictures Series (IAPS)118 and from the web. Alcohol and neutral pictures will be matched for color and complexity as well as other potentially important confounds (e.g., presence of people). The investigators will examine responses to approximately 100 trials each of alcohol pictures and control pictures in a mixed event design (\ 15 minutes), in order to reduce predictability of the picture type. After viewing pictures participants reported craving for alcohol on a scale from 1 to 9 (1=no craving, 9=extreme craving) with higher scores indicating worse outcomes. |
| Reductions in Self-reported Craving | 2 months following treatment | Self-reported craving will be measured using the Penn Alcohol Craving Scale (scaled from 0 to 5 with higher scores indicate worse outcome = more craving) with higher scores mean a worse outcome. |
| Improvements in Inhibitory Control | Post-treatment | To examine inhibitory control, the investigators will use a Stop Signal Task in which participants make left-right judgments of the directionality of an arrow presented on the screen. For each trial, a circle will appear for 500 ms, followed by a left or right-pointing arrow for up to 1 second and between 500 ms and 2500 ms jittered inter-trial interval to reduce anticipatory responses. Approximately 25% of trials will be stop trials with a tone played to signal participants to inhibit the current response. This timing of the tone is dynamically adjusted to ensure successful inhibition on approximately 50% of trials. There will be 240 trials across 6 blocks (\ 10 minutes). Inhibitory control is measured by stop signal reaction time. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Stimulation With Mindfulness Brain stimulation with mindfulness-based relapse prevention. Treatment sessions will be 2 hours for 8 sessions, with the first 30 minutes consisting of transcranial direct current stimulation (tDCS) with the current set to 2.0 milliamps (mA) and guided meditation practice.
Brain stimulation with mindfulness-based relapse prevention: Participants will participate in weekly or twice weekly group mindfulness based relapse prevention (MBRP) + transcranial direct current stimulation (tDCS) intervention sessions for up to eight weeks. All participants will receive 8 two hour sessions of MBRP + tDCS, regardless of the group schedule. Subjects will receive 30 minutes of either active or sham tDCS stimulation, depending on their group assignment. After tDCS, sessions will include discussions of mindfulness as a means of coping with craving, cognitions, and emotions, role play exercises, and mindfulness practice. | 47 |
| Sham Brain Stimulation With Mindfulness Brain stimulation with mindfulness-based relapse prevention. Treatment sessions will be 2 hours for 8 sessions, with the first 30 minutes consisting of transcranial direct current stimulation (tDCS) with the current set to ramp up to 2.0 milliamps (mA) and then ramp down to 0.0 mA and guided meditation practice.
Brain stimulation with mindfulness-based relapse prevention: Participants will participate in weekly or twice weekly group mindfulness based relapse prevention (MBRP) + transcranial direct current stimulation (tDCS) intervention sessions for up to eight weeks. All participants will receive 8 two hour sessions of MBRP + tDCS, regardless of the group schedule. Subjects will receive 30 minutes of either active or sham tDCS stimulation, depending on their group assignment. After tDCS, sessions will include discussions of mindfulness as a means of coping with craving, cognitions, and emotions, role play exercises, and mindfulness practice. | 37 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 6 |
| Overall Study | Withdrawal by Subject | 5 | 8 |
Baseline characteristics
| Characteristic | Active Stimulation With Mindfulness | Sham Brain Stimulation With Mindfulness | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 33 Participants | 74 Participants |
| Age, Continuous | 51.43 years STANDARD_DEVIATION 14.19 | 53.35 years STANDARD_DEVIATION 11.41 | 52.27 years STANDARD_DEVIATION 13 |
| Drinks per Drinking Occasion | 6.64 drinks per drinking occasion STANDARD_DEVIATION 3.54 | 6.92 drinks per drinking occasion STANDARD_DEVIATION 4.35 | 6.76 drinks per drinking occasion STANDARD_DEVIATION 3.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 16 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 21 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) White | 32 Participants | 22 Participants | 54 Participants |
| Region of Enrollment United States | 47 participants | 37 participants | 84 participants |
| Sex: Female, Male Female | 19 Participants | 15 Participants | 34 Participants |
| Sex: Female, Male Male | 28 Participants | 22 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 37 |
| other Total, other adverse events | 0 / 47 | 0 / 37 |
| serious Total, serious adverse events | 0 / 47 | 0 / 37 |
Outcome results
Primary
Drinks Per Drinking Day
The Form 90 will be used to derive estimates of the primary outcome: drinks (standard drink=14 grams of pure alcohol) per drinking day.
Time frame: Post-treatment and 2-month follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Stimulation With Mindfulness | Drinks Per Drinking Day | Post-treatment assessment | 5.12 drinks per drinking day | Standard Deviation 3.14 |
| Active Stimulation With Mindfulness | Drinks Per Drinking Day | 2-month follow-up | 4.95 drinks per drinking day | Standard Deviation 3.18 |
| Sham Brain Stimulation With Mindfulness | Drinks Per Drinking Day | Post-treatment assessment | 5.64 drinks per drinking day | Standard Deviation 4.06 |
| Sham Brain Stimulation With Mindfulness | Drinks Per Drinking Day | 2-month follow-up | 5.48 drinks per drinking day | Standard Deviation 4.28 |
Secondary
Percent Heavy Drinking Days
The Form 90 will be used to derive estimates of the secondary outcome: percent heavy drinking days, where heavy drinking is defined as 4+ drinks per occasion for women and 5+ drinks per occasion for men.
Time frame: Post-treatment and 2-month follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Stimulation With Mindfulness | Percent Heavy Drinking Days | Post-treatment assessment | 27.42 percentage of heavy drinking days | Standard Deviation 30.54 |
| Active Stimulation With Mindfulness | Percent Heavy Drinking Days | 2-month follow-up | 29.51 percentage of heavy drinking days | Standard Deviation 31.15 |
| Sham Brain Stimulation With Mindfulness | Percent Heavy Drinking Days | Post-treatment assessment | 25.93 percentage of heavy drinking days | Standard Deviation 26.82 |
| Sham Brain Stimulation With Mindfulness | Percent Heavy Drinking Days | 2-month follow-up | 28.80 percentage of heavy drinking days | Standard Deviation 33.16 |
Other Pre-specified
Cue Reactivity at the Post-Treatment Assessment
To measure cue reactivity to alcohol, the investigators will use a visual cue presentation task. Participants will view pictures of alcohol containing beverages and neutral pictures from the International Affective Pictures Series (IAPS)118 and from the web. Alcohol and neutral pictures will be matched for color and complexity as well as other potentially important confounds (e.g., presence of people). The investigators will examine responses to approximately 100 trials each of alcohol pictures and control pictures in a mixed event design (\ 15 minutes), in order to reduce predictability of the picture type. After viewing pictures participants reported craving for alcohol on a scale from 1 to 9 (1=no craving, 9=extreme craving) with higher scores indicating worse outcomes.
Time frame: Post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Stimulation With Mindfulness | Cue Reactivity at the Post-Treatment Assessment | 3.49 Score on a scale | Standard Deviation 1.81 |
| Sham Brain Stimulation With Mindfulness | Cue Reactivity at the Post-Treatment Assessment | 3.06 Score on a scale | Standard Deviation 1.61 |
Other Pre-specified
Improvements in Inhibitory Control
To examine inhibitory control, the investigators will use a Stop Signal Task in which participants make left-right judgments of the directionality of an arrow presented on the screen. For each trial, a circle will appear for 500 ms, followed by a left or right-pointing arrow for up to 1 second and between 500 ms and 2500 ms jittered inter-trial interval to reduce anticipatory responses. Approximately 25% of trials will be stop trials with a tone played to signal participants to inhibit the current response. This timing of the tone is dynamically adjusted to ensure successful inhibition on approximately 50% of trials. There will be 240 trials across 6 blocks (\ 10 minutes). Inhibitory control is measured by stop signal reaction time.
Time frame: Post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Stimulation With Mindfulness | Improvements in Inhibitory Control | 284.43 milliseconds | Standard Deviation 94.85 |
| Sham Brain Stimulation With Mindfulness | Improvements in Inhibitory Control | 266.06 milliseconds | Standard Deviation 51.07 |
Other Pre-specified
Reductions in Self-reported Craving
Self-reported craving will be measured using the Penn Alcohol Craving Scale (scaled from 0 to 5 with higher scores indicate worse outcome = more craving) with higher scores mean a worse outcome.
Time frame: 2 months following treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Stimulation With Mindfulness | Reductions in Self-reported Craving | 2.24 Score on a scale | Standard Deviation 1.21 |
| Sham Brain Stimulation With Mindfulness | Reductions in Self-reported Craving | 2.40 Score on a scale | Standard Deviation 1.42 |