Effect of High-Intensity Transcranial Alternating Current Stimulation on Gambling Disorder: A Randomized Controlled Trial (HITACSRCT-GD)

The investigators assume that transcranial Alternating Current Stimulation (tACS) could improve gambling disorder patients' executive-control function by adjusting the synchronization patterns and enhancing the functional connectivity of the prefrontal-ventral striatum pathway. This study intends to validate the effect of tACS treatment, which has been discovered in the previous pilot study. Three-month follow-up assessment will be conducted to test the changing of the executive-control function and its mechanism.

Study Overview

• Status: Not yet recruiting
• Conditions: Gambling Disorder
• Intervention / Treatment: Device: HI-tACS; Device: Sham stimulation

Detailed Description

Gambling disorder is become a major social and public health problem in China. Executive-control dysfunction is the main symptom of behavioral addiction like gambling disorder. Previous studies have demonstrated the relationship between cognitive dysfunction and prefrontal-ventral striatum pathway. Studies have shown that abnormal phase synchronization and phase-amplitude coupling (PAC) induced the impairment of cognition, and transcranial Alternating Current Stimulation (tACS) could improve executive-control function by adjusting the abnormal synchronization. However, it has not been verified among gambling disorder patients. The investigators assume that tACS could improve gambling disorder patients' executive-control function by adjusting the synchronization patterns and enhancing the functional connectivity of the prefrontal-ventral striatum pathway. This study intends to test the effect of tACS treatment, which has been discovered in the previous pilot study. Three-month follow-up assessment will be conducted to test the changing of the executive-control function and its mechanism. This study will provide a practical and theoretical basis for developing a novel treatment for gambling disorder.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiang Du, MD, PhD.; Phone Number: +8602164906315; Email: dujiangdou@163.com

Study Locations

• China
  • Shanghai, China
    • Shanghai Mental Health Center
    • Contact: Jiang Du, MD, PhD.; Phone Number: +86 021 6490 6315; Email: dujiangdou@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18-60, male or female, with 9 or more years of education, and able to complete questionnaire evaluation and behavioral tests;
• Meet DSM-5 (Diagnostic and Statistical Manual of mental disorders，DSM) diagnostic criteria for gambling disorder;
• Have gambled for at least one year (at least once a week);
• Normal vision and hearing, or within the normal range after correction;
• Agree to cooperate in the follow-up evaluation;
• No metal implantation in the head, no history of nerve problems or head injury, and no skin sensitivity.

Exclusion Criteria:

• Have severe cognitive impairment, such as a history of head trauma, -cerebrovascular disease, epilepsy, etc.;
• Have used drugs promoting cognitive function in the last 6 months;
• Have impaired intelligence (Intelligence Quotient<70);
• Abuse or dependence of psychoactive substances (except nicotine) in the last 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group for gambling addiction; A 40-minute transcranial alternating current stimulus intervention of real stimulus is conducted twice a day (at least 3 hours apart) for a total of 10 days in the intervention group of gambling addiction.	Device: HI-tACS; Three conductive electrodes are placed overhead. In the 10/20 international placement system, a 4.45 9.53 cm electrode is placed on the forehead corresponding to Fpz, Fp1 and Fp2. Two 3.18 3.81 cm electrodes are placed on the mastoid region of each side. The tACS stimulation waveform includes ramp-up and ramp-down periods of 180 and 12 s, respectively. The frequency of stimulation is 77.5Hz, and the current is 15mA.
Sham Comparator: Sham stimulation; A 40-minute transcranial alternating current stimulus intervention of sham stimulus is conducted twice a day (at least 3 hours apart) for a total of 10 days in the intervention group of gambling addiction.	Device: Sham stimulation; Three conductive electrodes are placed overhead. In the 10/20 international placement system, a 4.45 9.53 cm electrode is placed on the forehead corresponding to Fpz, Fp1 and Fp2. Two 3.18 3.81 cm electrodes are placed on the mastoid region of each side. The appearance of the above-mentioned equipment is identical to that of the real stimulation group devices, but it only simulates the electrical sensation produced at the beginning and end of stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the gambling symptoms	Gambling symptom severity will be measured by the Pathological Gambling Yale-Brown Obsessive Compulsive Scale (PG-YBOCS). The total score of PG-YBOCS ranges from 0 to 40, in which higher scores indicate more severe pathological gambling symptoms.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the risky decision-making performance	Risky decision-making performance will be assessed using the Balloon Analogue Risk Task (BART). Higher average pumps in the BART indicate greater risk-taking propensity. Feedback-related negativity (FRN) will be recorded using electroencephalography (EEG), with larger amplitude typically reflecting enhanced sensitivity to negative feedback. Pig dice game will be administered during functional magnetic resonance imaging (fMRI) scanning to assess risk-taking decision-making. Higher frequency of continued dice rolls indicates greater risk propensity. Neural activity in the prefrontal cortex and striatum will be analyzed, with increased activation typically associated with risk evaluation and reward processing.	Baseline, two weeks after the intervention.
Change of the inhibitory control performance	Stop-signal task (SST) will be employed to measure inhibitory control. Longer stop-signal reaction times (SSRT) indicate poorer response inhibition. The N2/P3 components will be recorded using electroencephalography (EEG), with enhanced N2 amplitude and reduced P3 amplitude typically reflecting greater cognitive conflict and inhibitory processing efficiency, respectively.	Baseline, two weeks after the intervention.
Change of the resting state neural activity.	Resting-state functional magnetic resonance imaging (rsfMRI) will be used to assess intrinsic brain connectivity. Lower amplitude of low-frequency fluctuations (ALFF) and reduced functional connectivity (FC) within the default mode network (DMN) may reflect altered neural efficiency. Resting-state electroencephalography (rsEEG) will be employed to measure spontaneous neural oscillations. Enhanced theta/beta ratio and reduced alpha power may indicate compromised regulatory control and cortical arousal, respectively.	Baseline, two weeks after the intervention.
Change of depressive symptoms	Depressive symptoms will be measured by the 17-item Hamilton Depression Rating Scale (HAMD-17). The total score of HAMD-17 ranges from 0 to 52, in which higher scores mean a higher severity of depressive symptoms.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention
Change of anxiety symptoms	Anxiety symptoms will be measured by the 14-item Hamilton Anxiety Rating Scale (HAMA-14). The total score of HAMA-14 ranges from 0 to 56, in which higher scores mean a higher severity of anxiety symptoms.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention
Change of the sleep quality	Sleep quality will be measured by the Pittsburgh Sleep Quality Index (PSQI). The total score of PSQI ranges from 0 to 21, in which higher scores mean poorer sleep quality.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention
Change of the gambling craving	Gambling craving will be measured by the gambling craving Visual Analog Scale (VAS). The total score of VAS ranges from 0 to 10, in which higher scores mean a higher level of gambling craving.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention
Side effect of the modulation	Side effects will be measured by the Treatment Emergent Symptom Scale (TESS). The total score of TESS varies depending on symptom severity, in which higher scores indicate more significant adverse reactions.	Immediately after the intervention
Change of the self-control ability	Self-control ability will be measured by the Self-Control Scale (SCS). Higher scores of SCS indicate better self-regulation and impulse control.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention
Change of the gambling symptom severity	Gambling symptom severity will be measured by the Gambling Symptom Assessment Scale (G-SAS). The total score of G-SAS ranges from 0 to 48, in which higher scores mean more severe gambling-related symptoms.	Baseline, immediately after the intervention, two weeks after the intervention, one month after the intervention, two months after the intervention, three months after the intervention

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 28, 2026

Study Registration Dates

• First Submitted: November 10, 2025
• First Submitted That Met QC Criteria: November 12, 2025
• First Posted (Estimated): November 14, 2025

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: High-Intensity Transcranial Alternating Current Stimulation, Gambling disorder.
• Additional Relevant MeSH Terms: Mental Disorders; Disruptive, Impulse Control, and Conduct Disorders; Behavior; Risk-Taking; Gambling
• Other Study ID Numbers: JDu-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No