Behavioral FlexibilityFLAMENCT06634771

Flexibility, Alcohol Misuse, and Excitation

A study testing 10 Hz transcranial alternating current stimulation (tACS) in people with Behavioral Flexibility and Healthy Volunteers, run by University of North Carolina, Chapel Hill at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 22 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Behavioral Flexibility, Healthy Volunteers, High Risk Alcohol Use
What is being tested?: 10 Hz transcranial alternating current stimulation (tACS)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 18 Jul 2024to 24 Jan 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 22 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

• 22-50 years old
Have a high school diploma or equivalent
Medically healthy
Fluent in English
For RISK group only:
High risk alcohol use in the past month [World Health Organization (WHO ) risk level 2-4]

Show all 14Show fewer

No history of adolescent binge drinking
For RISK+ Adolescent binge alcohol (AIE) group only:
High risk alcohol use in the past month (WHO risk level 2-4)
High levels of adolescent alcohol use (4 or more binge drinking episodes before age 18)
For Control (CON) group only:
Low risk alcohol use throughout the lifetime (WHO risk level 0-1)
No history of adolescent binge drinking
No lifetime history of Alcohol Use Disorder (AUD)

Who cannot join

Any individual who meets one or more of the following criteria will be excluded from participation [excluding positive breath alcohol concentration (BAC), urine drug screen, psychiatric diagnoses, and color blindness, all will be self-reported]:
Lifetime history of a substance use disorder (SUD; including nicotine) but participants will not be excluded for an AUD.
Neurological disease such as dementia, seizures or head trauma
History of psychosis or psychotic episodes
Diagnosis of attention deficit hyperactivity disorder (ADHD)
Any systemic or inflammatory disease that could affect cognitive functioning (e.g., cancer, cardiovascular disease)

Show all 20Show fewer

Any motor or visual disturbances that could hinder task performance (e.g., color blindness)
Use of psychoactive recreational drugs in the past month (excluding caffeine and alcohol)
Use of psychotropic medications in the past month including antidepressants, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics (excluding antidepressant use when dosage has been stable for 1 month or longer)
Use of therapeutic brain stimulation [e.g. transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT)] in the past month
Any history of brain surgery
History of migraine headaches
Pregnancy
Any brain implants or devices
First degree relative with primary epilepsy
Claustrophobia
Any magnetic resonance imaging (MRI) contraindication based on the University of North Carolina Biomedical Research Imaging Center's MRI safety checklist
Breath alcohol above 0.0% at time of session
Positive urine drug screen at time of session
If a participant should have an exclusion criterion arise in the course of their participation (e.g. pregnancy or psychotic episode), their participation in the study will end unless the circumstances are transitory in nature (e.g. positive breath alcohol or urine drug screen).

Trial locations and contacts

1 site in 1 country.

United States1 site

University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: Frontal E/I Balance Mediation of tACS Effects on Behavioral Flexibility

The goal of this study is to learn whether a single non-invasive brain stimulation alpha-transcranial alternating current stimulation (alpha-tACS) session changes measures of excitability in the prefrontal cortex. It will also learn whether these changes predict differences in habitual action selection in a laboratory task and whether the effects depend on alcohol use history. The main questions it aims to answer are:

Does alpha-tACS reduce habitual action selection by reducing excitability in the prefrontal cortex? Is alpha-tACS most effective in reducing habitual action selection in hazardous drinkers who engaged in binge-drinking during adolescence?

Researchers will compare alpha-tACS to sham stimulation to see if alpha-tACS changes habitual action selection by changing prefrontal excitability.

Participants will:

Visit the lab for behavioral training Visit the imaging center for an MRI session Visit the lab to receive alpha-tACS or sham stimulation during behavioral testing and undergo EEG recordings before and after stimulation Visit the imaging center for a repeat MRI session Provide a small sample of blood from a finger-prick in the first and last visits.

Read the detailed description

This study is designed to probe the role of the balance between excitatory (E) and inhibitory (I) signaling (E/I) in key nodes of control circuitry in mediating the relationship between alcohol misuse and inflexible behavior. In addition, the investigators aim to determine whether adolescent binge alcohol exposure amplifies the effects of binge exposure in adulthood. The investigators will accomplish this goal via a single multi-session study. Participants (n=66) will comprise three groups: adults self-reporting high risk drinking [World Health Organization (WHO) risk levels 2, 3, or 4], with (n=22) or without (n=22) a history of adolescent alcohol misuse (AIE), and lifetime low risk drinking adults (WHO risk levels 0 or 1; n=22).

Design: a 3-session study that includes an initial screening session and behavioral training (Session 1), behavioral testing and a magnetic resonance imaging (MRI) scan session (Session 2), bifrontal 10Hz-transcranial alternating current stimulation (tACS; true or sham) during behavioral testing with pre- and post-electroencephalogram (EEG) recording in a resting-state, followed by a second MRI scan session (Session 3). The investigators predict that adolescent and adult binge history will have interacting effects on E/I balance indices derived from EEG and magnetic resonance spectroscopy (MRS) and on behavioral flexibility measured in the Hidden Association between Images Task (HABIT) Test and that E/I balance indices will mediate the relationship between alcohol misuse and behavioral flexibility. The investigators also propose to test a causal relationship between E/I balance and behavioral flexibility by testing whether 10Hz-tACS to bilateral dorsolateral prefrontal cortex (dlPFC) alters habitual action selection in the HABIT Test in proportion to its effects on the dlPFC 1/f EEG slope and/or the MRS-derived gamma-amino-butyric acid (GABA)/glutamate+glutamine (Glx) ratio. The investigators predict that changes in indices of E/I balance induced by tACS will inversely associate with changes in habitual response selection. The investigators will collect a small amount of blood from a finger prick in Sessions 1 and 3 will use the collected dried blood spots to measure inflammatory markers.

Conditions: Behavioral Flexibility, Healthy Volunteers, High Risk Alcohol Use
Being tested: 10 Hz transcranial alternating current stimulation (tACS), sham transcranial alternating current stimulation (tACS)
Keywords: alcohol, brain stimulation, MRI, EEG

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

10 Hz transcranial alternating current stimulation (tACS)Other
10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds.
sham transcranial alternating current stimulation (tACS)Other
Sham tACS: The procedure for sham stimulation will be identical, but it will last for 2 minutes instead of 30 minutes.

Study groups in NCT06634771
Study group	Role	What they receive
10Hz bi-frontal tACS	Experimental	For Session 3, participants will complete a Habitual Association between Images Task (HABIT) Test Session in the Howell Hall Neurostimulation Core Lab or electroencephalogram (EEG) Core Lab, which is located one floor below the Boettiger Lab. Participants will receive either 10Hz bi-frontal transcranial alternating current stimulation (tACS) or sham tACS. 10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds. Receives: Other: 10 Hz transcranial alternating current stimulation (tACS)
sham tACS	Sham comparator	Sham transcranial alternating current stimulation (tACS): The procedure for sham stimulation will be identical, but the actual stimulation will last for 2 minutes instead of 30 minutes. Participants generally report that stimulation is felt most strongly at the beginning of active stimulation, before they adjust to the sensation. Sham stimulation is meant to mimic this progression in terms of tactile salience. Stimulation is delivered for 2 minutes at the beginning of the HABIT reversal task, flanked by 10 second linear envelope ramps. The stimulating electrodes are left on the head until completion of the HABIT task, as is the case in active stimulation. There is no visual or auditory indication to the participant or researcher when the 2-minute sham stimulation period has ended, allowing the sham stimulation condition to feel similar to active stimulation. Receives: Other: sham transcranial alternating current stimulation (tACS)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Proportion of Errors
In the HABIT task participants are trained to associate abstract images on the computer screen with specific responses (button presses). They initially learn two stimulus-response pairings and then practice these two pairings at the beginning of each session; these are referred to as the familiar (FAM) sets. At sessions 2 and 3 they also learn two new stimulus-response pairings, which are referred to as the novel (NOV) sets and which they do not encounter at later sessions. During sessions 2 and 3 they undergo a reversal test, during which the correct responses for one familiar set and one novel set are changed, and they must learn the new correct responses by trial and error. The outcome measure here is the proportion of total errors made in response to the devalued familiar set during the reversal test that are perseverative errors, or errors in which they respond with a button press that was previously correct but is no longer correct.
Measured: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
Change in Prefrontal GABA:Glutamate/Glutamine Ratio
The researchers will evaluate the difference in the gamma-aminobutyric acid (GABA):glutamate/glutamine ratios in the left dorsolateral prefrontal cortex, measured via single voxel magnetic resonance spectroscopy (MRS) at rest.
Measured: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

Secondary outcomes (6)

Change in C-reactive Protein
The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on C-reactive protein.
Measured: Baseline, study completion (an average of 2 weeks)
Change in Interleukin-6 (IL-6)
The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on interleukin-6 (IL-6).
Measured: Baseline, study completion (an average of 2 weeks)
Change in Tumor Necrosis Factor-alpha (TNF-alpha)
The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on tumor necrosis factor-alpha (TNF-alpha).
Measured: Baseline, study completion (an average of 2 weeks)
Change in Functional Connectivity Between the Bilateral dlPFC and the aIC
The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and anterior insular cortex (aIC) was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation.
Measured: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
Change in Functional Connectivity Between the dlPFC and Limbic Striatum
The effect of 10Hz-tACS on resting-state functional connectivity between the bilateral dorsolateral prefrontal cortex (dlPFC) and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation.
Measured: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
Change in Functional Connectivity Between aIC and Limbic Striatum
The effect of 10Hz-tACS on resting-state functional connectivity between the aIC and limbic striatum was quantified as the Fisher Z-transformed Pearson correlation coefficient. The BOLD timeseries for regions of interest were first extracted and then transformed into Z-scores using the Fisher r-to-z transformation. The Z-score represents the number of standard deviations away from the mean of the functional connectivity distribution. A Z-score of 0 represents the mean connectivity in the sample, with positive values indicating greater connectivity after stimulation, and a negative Z-score indicating less connectivity after stimulation.
Measured: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jul 202424 Jan 2025

First posted10 Oct 2024
Study start18 Jul 2024
Primary completion24 Jan 2025
Study completion24 Jan 2025

Why it stopped: The study was terminated due to the death of the Principal Investigator.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (32)Papers the sponsor has linked to this study.
Other trials for Behavioral FlexibilityStudies of the same condition, open and under way.
More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Model description: Study design consists of 3 groups of participants: 1. Control (CON): no adolescent binge drinking (AIE) and current (past month) World Health Organization (WHO) risk drinking levels of either 0 or 1 (abstinent or low-risk) 2. (RISK): no AIE and current WHO level 2, 3, or 4 (medium risk, high risk, or very high risk) 3. (RISK+AIE): history of adolescent binge drinking and current WHO risk level 2, 3, or 4. Within each group (n=22), participants will be randomly assigned to either the 10Hz tACS (stim) group or the sham tACS (sham) group. Study design requires randomly assigning individuals to a stimulation group after completing Session 1. Prior to study onset, Dr. Boettiger will create a randomization table in which stimulation type (true or sham) is pseudo randomly ordered within groups, stratified by sex. Dr. Boettiger will provide assignment to the study team based on this predefined randomization table in order to ensure balanced sex and group for each stimulation type.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06634771
Sponsor's protocol ID: 23-1702
Other IDs: P60AA011605
Acronym: FLAME
Status last verified: Jan 2026
First submitted: 3 Oct 2024
Last updated: 27 Mar 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Brief summary of the assessment schedule for data that will eventually be shared with the NIAAADA: In this 3-visit study, eligibility is first determined at the screening and randomization visit; dried blood spot measures of inflammatory markers will also be collected. In visit 2, measures of baseline habitual action selection in the HABIT, structural MRI, baseline resting-state fMRI, and single-voxel MRS measuring GABA and glutamate/glutamine will be collected. At visit 3, resting-state EEG before and after 10Hz- or sham-tACS, as well as habitual action selection in the HABIT during 10Hz- or sham-tACS, as well as repeat structural and functional MRI and MRS, and dried blood spot collection following 10Hz- or sham-tACS will be collected. Demographic, psychometric, and substance-related information will be collected via REDCap at the participant's convenience. Data will be uploaded to the PI's NIMH Data Archive (NDA) account by established deadlines.

Publications

Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One. 2010 Nov 1;5(11):e13766. doi: 10.1371/journal.pone.0013766.
PubMed 21072168
Wood W, Runger D. Psychology of Habit. Annu Rev Psychol. 2016;67:289-314. doi: 10.1146/annurev-psych-122414-033417. Epub 2015 Sep 10.
PubMed 26361052
Viner RM, Taylor B. Adult outcomes of binge drinking in adolescence: findings from a UK national birth cohort. J Epidemiol Community Health. 2007 Oct;61(10):902-7. doi: 10.1136/jech.2005.038117.
PubMed 17873228
Vanderhasselt MA, De Raedt R, Brunoni AR, Campanha C, Baeken C, Remue J, Boggio PS. tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli. PLoS One. 2013 May 21;8(5):e62219. doi: 10.1371/journal.pone.0062219. Print 2013.
PubMed 23704874
Smittenaar P, FitzGerald TH, Romei V, Wright ND, Dolan RJ. Disruption of dorsolateral prefrontal cortex decreases model-based in favor of model-free control in humans. Neuron. 2013 Nov 20;80(4):914-9. doi: 10.1016/j.neuron.2013.08.009. Epub 2013 Oct 24.
PubMed 24206669
Siqueira L, Smith VC; COMMITTEE ON SUBSTANCE ABUSE. Binge Drinking. Pediatrics. 2015 Sep;136(3):e718-26. doi: 10.1542/peds.2015-2337.
PubMed 26324872
Sellers KK, Mellin JM, Lustenberger CM, Boyle MR, Lee WH, Peterchev AV, Frohlich F. Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test. Behav Brain Res. 2015 Sep 1;290:32-44. doi: 10.1016/j.bbr.2015.04.031. Epub 2015 Apr 28.
PubMed 25934490
Rehm J, Shield KD, Roerecke M, Gmel G. Modelling the impact of alcohol consumption on cardiovascular disease mortality for comparative risk assessments: an overview. BMC Public Health. 2016 Apr 28;16:363. doi: 10.1186/s12889-016-3026-9.
PubMed 27121289
Ostlund SB, Balleine BW. Lesions of medial prefrontal cortex disrupt the acquisition but not the expression of goal-directed learning. J Neurosci. 2005 Aug 24;25(34):7763-70. doi: 10.1523/JNEUROSCI.1921-05.2005.
PubMed 16120777
Olsen RW, Liang J. Role of GABAA receptors in alcohol use disorders suggested by chronic intermittent ethanol (CIE) rodent model. Mol Brain. 2017 Sep 20;10(1):45. doi: 10.1186/s13041-017-0325-8.
PubMed 28931433
Miller EK, Cohen JD. An integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001;24:167-202. doi: 10.1146/annurev.neuro.24.1.167.
PubMed 11283309
McKim TH, Dove SJ, Robinson DL, Frohlich F, Boettiger CA. Addiction history moderates the effect of prefrontal 10-Hz transcranial alternating current stimulation on habitual action selection. J Neurophysiol. 2021 Mar 1;125(3):768-780. doi: 10.1152/jn.00180.2020. Epub 2020 Dec 23.
PubMed 33356905
McKim TH, Bauer DJ, Boettiger CA. Addiction History Associates with the Propensity to Form Habits. J Cogn Neurosci. 2016 Jul;28(7):1024-38. doi: 10.1162/jocn_a_00953. Epub 2016 Mar 11.
PubMed 26967944
Matsumoto H, Ugawa Y. Adverse events of tDCS and tACS: A review. Clin Neurophysiol Pract. 2016 Dec 21;2:19-25. doi: 10.1016/j.cnp.2016.12.003. eCollection 2017.
PubMed 30214966
Lam NH, Borduqui T, Hallak J, Roque A, Anticevic A, Krystal JH, Wang XJ, Murray JD. Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model. J Neurosci. 2022 Feb 9;42(6):1035-1053. doi: 10.1523/JNEUROSCI.1371-20.2021. Epub 2021 Dec 9.
PubMed 34887320

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Frontal E/I Balance Mediation of tACS Effects on Behavioral Flexibility
ClinicalTrials.gov ID: NCT06634771
Acronym / sponsor ID: FLAME / 23-1702
Conditions: Behavioral Flexibility, Healthy Volunteers, High Risk Alcohol Use
Keywords: alcohol, brain stimulation, MRI, EEG
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated due to the death of the Principal Investigator.
Enrolment: 7 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study start: 18 Jul 2024 (actual)
Primary completion: 24 Jan 2025 (actual)
Study completion: 24 Jan 2025 (actual)
First posted: 10 Oct 2024 (actual)
Results: Posted 27 Mar 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Researchers will compare alpha-tACS to sham stimulation to see if alpha-tACS changes habitual action selection by changing prefrontal excitability.

Participants will:

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2
Model description: Study design consists of 3 groups of participants: 1. Control (CON): no adolescent binge drinking (AIE) and current (past month) World Health Organization (WHO) risk drinking levels of either 0 or 1 (abstinent or low-risk) 2. (RISK): no AIE and current WHO level 2, 3, or 4 (medium risk, high risk, or very high risk) 3. (RISK+AIE): history of adolescent binge drinking and current WHO risk level 2, 3, or 4. Within each group (n=22), participants will be randomly assigned to either the 10Hz tACS (stim) group or the sham tACS (sham) group. Study design requires randomly assigning individuals to a stimulation group after completing Session 1. Prior to study onset, Dr. Boettiger will create a randomization table in which stimulation type (true or sham) is pseudo randomly ordered within groups, stratified by sex. Dr. Boettiger will provide assignment to the study team based on this predefined randomization table in order to ensure balanced sex and group for each stimulation type.

Arm	Type	Receives
10Hz bi-frontal tACS	Experimental	Other: 10 Hz transcranial alternating current stimulation (tACS)For Session 3, participants will complete a Habitual Association between Images Task (HABIT) Test Session in the Howell Hall Neurostimulation Core Lab or electroencephalogram (EEG) Core Lab, which is located one floor below the Boettiger Lab. Participants will receive either 10Hz bi-frontal transcranial alternating current stimulation (tACS) or sham tACS. 10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds.
sham tACS	Sham comparator	Other: sham transcranial alternating current stimulation (tACS)Sham transcranial alternating current stimulation (tACS): The procedure for sham stimulation will be identical, but the actual stimulation will last for 2 minutes instead of 30 minutes. Participants generally report that stimulation is felt most strongly at the beginning of active stimulation, before they adjust to the sensation. Sham stimulation is meant to mimic this progression in terms of tactile salience. Stimulation is delivered for 2 minutes at the beginning of the HABIT reversal task, flanked by 10 second linear envelope ramps. The stimulating electrodes are left on the head until completion of the HABIT task, as is the case in active stimulation. There is no visual or auditory indication to the participant or researcher when the 2-minute sham stimulation period has ended, allowing the sham stimulation condition to feel similar to active stimulation.

Who may qualify

Ages: 22 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

• 22-50 years old
High risk alcohol use in the past month [World Health Organization (WHO ) risk level 2-4]
No history of adolescent binge drinking
High risk alcohol use in the past month (WHO risk level 2-4)
High levels of adolescent alcohol use (4 or more binge drinking episodes before age 18)

Key exclusion criteria (20 listed)

Any individual who meets one or more of the following criteria will be excluded from participation [excluding positive breath alcohol concentration (BAC), urine drug screen, psychiatric diagnoses, and color blindness, all will be self-reported]:
If a participant should have an exclusion criterion arise in the course of their participation (e.g. pregnancy or psychotic episode), their participation in the study will end unless the circumstances are transitory in nature (e.g. positive breath alcohol or urine drug screen).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
10 Hz transcranial alternating current stimulation (tACS)10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds.	Other	10Hz bi-frontal tACS
sham transcranial alternating current stimulation (tACS)Sham tACS: The procedure for sham stimulation will be identical, but it will last for 2 minutes instead of 30 minutes.	Other	sham tACS

Primary outcome

Change in Proportion of Errors
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
In the HABIT task participants are trained to associate abstract images on the computer screen with specific responses (button presses). They initially learn two stimulus-response pairings and then practice these two pairings at the beginning of each session; these are referred to as the familiar (FAM) sets. At sessions 2 and 3 they also learn two new stimulus-response pairings, which are referred to as the novel (NOV) sets and which they do not encounter at later sessions. During sessions 2 and 3 they undergo a reversal test, during which the correct responses for one familiar set and one novel set are changed, and they must learn the new correct responses by trial and error. The outcome measure here is the proportion of total errors made in response to the devalued familiar set during the reversal test that are perseverative errors, or errors in which they respond with a button press that was previously correct but is no longer correct.
Change in Prefrontal GABA:Glutamate/Glutamine Ratio
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
The researchers will evaluate the difference in the gamma-aminobutyric acid (GABA):glutamate/glutamine ratios in the left dorsolateral prefrontal cortex, measured via single voxel magnetic resonance spectroscopy (MRS) at rest.

6 secondary outcomes

Change in C-reactive Protein
Time frame: Baseline, study completion (an average of 2 weeks)
Change in Interleukin-6 (IL-6)
Time frame: Baseline, study completion (an average of 2 weeks)
Change in Tumor Necrosis Factor-alpha (TNF-alpha)
Time frame: Baseline, study completion (an average of 2 weeks)
Change in Functional Connectivity Between the Bilateral dlPFC and the aIC
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
Change in Functional Connectivity Between the dlPFC and Limbic Striatum
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after
Change in Functional Connectivity Between aIC and Limbic Striatum
Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

Results and safety

Results posted to the registry on 27 Mar 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
10Hz Active tACS in Controls	3	3
Sham tACS in Controls	3	3
10Hz Active tACS in Current High-Risk Drinkers	0	0
Sham tACS in Current High-Risk Drinkers	1	1
10Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking	0	0
Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking	0	0

Primary outcome: Change in Proportion of Errors

Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after. Mean (Standard Deviation). Unit: proportion of perseverative errors

Measure	10Hz Active tACS in Controls n = 3	Sham tACS in Controls n = 3	10 Hz Active tACS in Current High-Risk Drinkers n = 0	Sham tACS in Current High-Risk Drinkers n = 1	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking n = 0	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking n = 0
Value	0.0898 (0.170)	-0.0299 (0.155)	–	0.0572	–	–

Population analysed: Study terminated prior to enrollment of participants into the "10 Hz Active tACS in Current High-Risk Drinkers," "10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking," or "Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking" Arms.

Primary outcome: Change in Prefrontal GABA:Glutamate/Glutamine Ratio

Time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after. Mean (Standard Deviation). Unit: ratio

Measure	10Hz Active tACS in Controls n = 3	Sham tACS in Controls n = 3	10 Hz Active tACS in Current High-Risk Drinkers n = 0	Sham tACS in Current High-Risk Drinkers n = 1	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking n = 0	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking n = 0
Value	11.87 (43.66)	5.37 (5.78)	–	.48 (0)	–	–

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the time of signing informed consent through study completion, up to two weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
10Hz Active tACS in Controls	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Sham tACS in Controls	0 of 3 (0%)	0 of 3 (0%)	0 of 3
10 Hz Active tACS in Current High-Risk Drinkers	0 of 0	0 of 0	0
Sham tACS in Current High-Risk Drinkers	0 of 1 (0%)	0 of 1 (0%)	0 of 1
10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking	0 of 0	0 of 0	0
Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21072168Zaehle T, Rach S, Herrmann CS. Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One. 2010 Nov 1;5(11):e13766. doi: 10.1371/journal.pone.0013766.
Background: PubMed 26361052Wood W, Runger D. Psychology of Habit. Annu Rev Psychol. 2016;67:289-314. doi: 10.1146/annurev-psych-122414-033417. Epub 2015 Sep 10.
Background: PubMed 17873228Viner RM, Taylor B. Adult outcomes of binge drinking in adolescence: findings from a UK national birth cohort. J Epidemiol Community Health. 2007 Oct;61(10):902-7. doi: 10.1136/jech.2005.038117.
Background: PubMed 23704874Vanderhasselt MA, De Raedt R, Brunoni AR, Campanha C, Baeken C, Remue J, Boggio PS. tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli. PLoS One. 2013 May 21;8(5):e62219. doi: 10.1371/journal.pone.0062219. Print 2013.
Background: PubMed 24206669Smittenaar P, FitzGerald TH, Romei V, Wright ND, Dolan RJ. Disruption of dorsolateral prefrontal cortex decreases model-based in favor of model-free control in humans. Neuron. 2013 Nov 20;80(4):914-9. doi: 10.1016/j.neuron.2013.08.009. Epub 2013 Oct 24.
Background: PubMed 26324872Siqueira L, Smith VC; COMMITTEE ON SUBSTANCE ABUSE. Binge Drinking. Pediatrics. 2015 Sep;136(3):e718-26. doi: 10.1542/peds.2015-2337.
Background: PubMed 25934490Sellers KK, Mellin JM, Lustenberger CM, Boyle MR, Lee WH, Peterchev AV, Frohlich F. Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test. Behav Brain Res. 2015 Sep 1;290:32-44. doi: 10.1016/j.bbr.2015.04.031. Epub 2015 Apr 28.
Background: PubMed 27121289Rehm J, Shield KD, Roerecke M, Gmel G. Modelling the impact of alcohol consumption on cardiovascular disease mortality for comparative risk assessments: an overview. BMC Public Health. 2016 Apr 28;16:363. doi: 10.1186/s12889-016-3026-9.
Background: PubMed 16120777Ostlund SB, Balleine BW. Lesions of medial prefrontal cortex disrupt the acquisition but not the expression of goal-directed learning. J Neurosci. 2005 Aug 24;25(34):7763-70. doi: 10.1523/JNEUROSCI.1921-05.2005.
Background: PubMed 28931433Olsen RW, Liang J. Role of GABAA receptors in alcohol use disorders suggested by chronic intermittent ethanol (CIE) rodent model. Mol Brain. 2017 Sep 20;10(1):45. doi: 10.1186/s13041-017-0325-8.
Background: PubMed 11283309Miller EK, Cohen JD. An integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001;24:167-202. doi: 10.1146/annurev.neuro.24.1.167.
Background: PubMed 33356905McKim TH, Dove SJ, Robinson DL, Frohlich F, Boettiger CA. Addiction history moderates the effect of prefrontal 10-Hz transcranial alternating current stimulation on habitual action selection. J Neurophysiol. 2021 Mar 1;125(3):768-780. doi: 10.1152/jn.00180.2020. Epub 2020 Dec 23.
Individual participant dataSharing planned: Yes. Brief summary of the assessment schedule for data that will eventually be shared with the NIAAADA: In this 3-visit study, eligibility is first determined at the screening and randomization visit; dried blood spot measures of inflammatory markers will also be collected. In visit 2, measures of baseline habitual action selection in the HABIT, structural MRI, baseline resting-state fMRI, and single-voxel MRS measuring GABA and glutamate/glutamine will be collected. At visit 3, resting-state EEG before and after 10Hz- or sham-tACS, as well as habitual action selection in the HABIT during 10Hz- or sham-tACS, as well as repeat structural and functional MRI and MRS, and dried blood spot collection following 10Hz- or sham-tACS will be collected. Demographic, psychometric, and substance-related information will be collected via REDCap at the participant's convenience. Data will be uploaded to the PI's NIMH Data Archive (NDA) account by established deadlines.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Charlotte A Boettiger, PhD principal investigator

University of North Carolina, Chapel Hill

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Proportion of Errors (time frame: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06634771, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.