Flexibility, Alcohol Misuse, and Excitation

NCT ID: NCT06634771

Last Updated: 2024-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-18

Study Completion Date

2027-11-30

Brief Summary

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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.

Detailed Description

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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

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Behavioral Flexibility Healthy Volunteers High Risk Alcohol Use

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
The study team will be provided a numeric code to enter into the XCSITE 100 tACS system, which will conceal the stimulation parameters from the study team, ensuring double blinding. The XSCITE 100 device allows for the programming of stimulation codes corresponding to sham or active stimulation, both of which are set to a total duration of 30 minutes, allowing for reliable double-blinding.

Study Groups

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10Hz bi-frontal 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.

Group Type EXPERIMENTAL

10 Hz transcranial alternating current stimulation (tACS)

Intervention Type DEVICE

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 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.

Group Type SHAM_COMPARATOR

sham transcranial alternating current stimulation (tACS)

Intervention Type DEVICE

Sham tACS: The procedure for sham stimulation will be identical, but it will last for 2 minutes instead of 30 minutes.

Interventions

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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.

Intervention Type DEVICE

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* • 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 \[World Health Organization (WHO ) risk level 2-4\]
* 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)

Exclusion Criteria

* 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)
* 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).
Minimum Eligible Age

22 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Charlotte Boettiger, PhD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Charlotte A Boettiger, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Charlotte A Boettiger, PhD

Role: CONTACT

919-962-2119

Grace M Elliott, MS

Role: CONTACT

919-843-9193

Facility Contacts

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Charlotte A Boettiger, PhD

Role: primary

919-962-2119

Grace M Elliott, MS

Role: backup

919-843-9193

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Other Identifiers

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P60AA011605

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-1702

Identifier Type: -

Identifier Source: org_study_id

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