Trial Outcomes & Findings for Flexibility, Alcohol Misuse, and Excitation (NCT NCT06634771)

Last Updated: 2026-03-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

Target enrollment

7 participants

Primary outcome timeframe

Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

Results posted on

2026-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	10Hz Active tACS in Controls Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants complete a Habitual Association between Images Task (HABIT) while receiving 10Hz bi-frontal transcranial alternating current stimulation (tACS) delivered via an XCSITE 100 device through electrodes placed over Cz, F3, and F4. Stimulation parameters consist of 2mA peak-to-peak 10Hz sine-wave with 10-second ramps in and out, lasting 30 minutes and 20 seconds during the second half of the HABIT task.	Sham tACS in Controls Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants complete a HABIT task while receiving sham tACS. Electrodes are placed identically to active stimulation (Cz, F3, F4), but actual stimulation lasts only 2 minutes at the task beginning with 10-second ramps. Electrodes remain on the head throughout the task to maintain blinding.	Sham tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants complete a HABIT task while receiving sham tACS. Electrodes are placed identically to active stimulation (Cz, F3, F4), but actual stimulation lasts only 2 minutes at the task beginning with 10-second ramps. Electrodes remain on the head throughout the task to maintain blinding.
Overall Study STARTED	3	3	1
Overall Study COMPLETED	3	3	1
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Flexibility, Alcohol Misuse, and Excitation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10Hz Active tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers n=1 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	Total n=7 Participants Total of all reporting groups
Age, Continuous	34.3 years STANDARD_DEVIATION 6.4 • n=56 Participants	34.0 years STANDARD_DEVIATION 10.4 • n=62 Participants	—	50 years n=53 Participants	—	—	36.4 years STANDARD_DEVIATION 9.3 • n=18 Participants
Sex: Female, Male Female	1 Participants n=56 Participants	2 Participants n=62 Participants	—	1 Participants n=53 Participants	—	—	4 Participants n=18 Participants
Sex: Female, Male Male	2 Participants n=56 Participants	1 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	3 Participants n=18 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	1 Participants n=18 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=56 Participants	3 Participants n=62 Participants	—	1 Participants n=53 Participants	—	—	6 Participants n=18 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) Asian	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) Black or African American	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) White	3 Participants n=56 Participants	3 Participants n=62 Participants	—	1 Participants n=53 Participants	—	—	7 Participants n=18 Participants
Race (NIH/OMB) More than one race	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=56 Participants	0 Participants n=62 Participants	—	0 Participants n=53 Participants	—	—	0 Participants n=18 Participants
Region of Enrollment United States	3 Participants n=56 Participants	3 Participants n=62 Participants	—	1 Participants n=53 Participants	—	—	7 Participants n=18 Participants

PRIMARY outcome

Timeframe: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

Population: 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.

Outcome measures

Outcome measures
Measure	10Hz Active tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers n=1 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.
Change in Proportion of Errors	0.0898 proportion of perseverative errors Standard Deviation 0.170	-0.0299 proportion of perseverative errors Standard Deviation 0.155	—	0.0572 proportion of perseverative errors	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	10Hz Active tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers n=1 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.
Change in Prefrontal GABA:Glutamate/Glutamine Ratio	11.87 ratio Standard Deviation 43.66	5.37 ratio Standard Deviation 5.78	—	.48 ratio Standard Deviation 0	—	—

SECONDARY outcome

Timeframe: Baseline, study completion (an average of 2 weeks)

Population: While the protocol was not modified, no post-stimulation blood samples were obtained due to session 3 time constraints. As a result, change-from-baseline values for the planned biomarker outcomes could not be generated. In addition, the baseline samples were not analyzed because the study team no longer had the required laboratory expertise or funding to conduct the assays following the death of the Principal Investigator.

The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on C-reactive protein.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, study completion (an average of 2 weeks)

The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on interleukin-6 (IL-6).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, study completion (an average of 2 weeks)

The researchers will measure the effect of transcranial alternating current stimulation (tACS) of bilateral dorsolateral prefrontal cortex on tumor necrosis factor-alpha (TNF-alpha).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

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.

Outcome measures

Outcome measures
Measure	10Hz Active tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers n=1 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.
Change in Functional Connectivity Between the Bilateral dlPFC and the aIC	-0.012066667 Z-transformed correlation coefficient Standard Deviation 0.181980805	0.0097 Z-transformed correlation coefficient Standard Deviation 0.085130312	—	-0.2278 Z-transformed correlation coefficient Standard Deviation 0	—	—

SECONDARY outcome

Timeframe: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

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.

Outcome measures

Outcome measures
Measure	10Hz Active tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Controls n=3 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 0 or 1 (abstinent or low-risk drinkers). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers n=1 Participants Participants have no history of adolescent binge drinking and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.	10 Hz Active tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received active 10Hz bi-frontal tACS.	Sham tACS in Current High-Risk Drinkers With Adolescent Binge Drinking Participants have a history of adolescent binge drinking (four or more binge episodes before age 18; per NIAAA criteria, a binge episode equals 4+ drinks in a 2-hour period for females and 5+ drinks in a 2-hour period for males) and current WHO risk drinking levels of 2, 3, or 4 (medium to very high risk). During Session 3, participants received sham bi-frontal tACS.
Change in Functional Connectivity Between the dlPFC and Limbic Striatum	0.071 Z-transformed correlation coefficient Standard Deviation 0.108360002	-0.065066667 Z-transformed correlation coefficient Standard Deviation 0.12092652	—	0.0134 Z-transformed correlation coefficient Standard Deviation 0	—	—

SECONDARY outcome

Timeframe: Pre-stimulation (Session 2) up to 2 weeks before, post-stimulation (Session 3), immediately after

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.