Effects of taVNS Combined With tACS on Adolescents With Non-Suicidal Self-Injury

NCT07486804 | Recruiting

• 1 other identifier: 81251050
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

NSSI behavior is highly prevalent among adolescents, and its mechanisms are closely associated with attentional bias toward self-injury-related information and impulsivity, both of which may be related to reduced dlPFC activation levels. Introducing taVNS as a priming stimulus to pre-regulate brain state and optimize subsequent tACS treatment response provides a novel approach to addressing inconsistent intervention effects. Simultaneously, this facilitates a shift in the brain from passive stimulus reception to active state regulation, offering important theoretical foundations for developing more precise and efficient cross-modal neuromodulation therapies.This study aims to systematically validate the efficacy of a combined protocol using taVNS as a priming modality followed by tACS over the left dlPFC through a randomized controlled trial (RCT). The investigators hypothesize that: ① Compared to tACS intervention alone, this combined approach will not only demonstrate non-inferiority in overall therapeutic efficacy but, more importantly, significantly reduce inter-individual variability in treatment response to tACS. This would mitigate the issue of high clinical response heterogeneity and enhance the stability and predictability of treatment outcomes. ② Early behavioral biomarkers of intervention response are anticipated: Immediate improvements in attentional bias following a single combined intervention session will significantly predict reductions in the frequency and intensity of Non-Suicidal Self-Injury (NSSI) after a full course (14 sessions) of treatment. This suggests that early positive changes in cognitive function could serve as valid indicators predicting long-term clinical efficacy, offering a critical time window for implementing individualized treatment adjustments. ③ The study will elucidate the effects of the taVNS-primed combined tACS treatment on neuroimaging mechanisms in adolescents with NSSI.

Conditions

Non-suicidal Self-injury

Keywords

non-suicidal self-injury; transcranial alternating current stimulation; taVNS; tACS; state-dependant

Outcome Measures

Primary Outcomes (5)

• Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ) reduction in the frequency of self-injury

  The ANSAQ is a brief, self-report tool specifically designed for adolescents aged 12-18 to quantify non-suicidal self-injury (NSSI) over the past year. It is used both to screen for clinically relevant self-harm and to track changes in self-injury frequency after an intervention. Higher frequencies indicate more severe NSSI behavior.

  Assessments were conducted at baseline (pre-treatment), as well as on day 1, at week 1, and at month 1 post-treatment.

• Brief Barratt Impulsiveness Scale (BBIS)

  The BBIS is an 8-item, self-report subset of the well-known Barratt Impulsiveness Scale. Each item (e.g., "I act on the spur of the moment") is answered on a 4-point scale: 1 = rarely/never, 2 = occasionally, 3 = often, 4 = almost always/always. Total scores range 8-32; higher scores indicate greater impulsivity. Total score: 32. Higher scores indicate greater impulsivity.

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• Eye movement index-fixation counts

  A free-viewing paradigm consisting of 60 images was employed, with eye movements recorded using an SMI-RED eye-tracking system. Each trial comprised a four-image array: three neutral stimuli and one NSSI-related stimulus, presented for 4000 ms. A dot-probe paradigm consisting of 204 trials was employed, with eye movements recorded using an SMI-RED eye-tracking system. Each trial comprised a pair of images: one neutral stimulus and one NSSI-related stimulus, presented for either 200 ms or 500 ms.The region of interest (ROI) was defined as the area containing the NSSI-related cue. 'Dwell time' was operationalized as the total duration (in milliseconds) that the eyes remained fixated within the ROI during image presentation. Values were averaged across all NSSI-related cue images at baseline (Day 0) and post-intervention (Day 8). A clinically relevant improvement in inhibitory control was defined as a ≥20% reduction in total dwell time on NSSI-related cues relative to baseline.

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• Stop Signal Task（SST）

  The experiment consisted of 192 trials (64 × 3), preceded by a 20-trial practice phase. Each trial began with a 1.5-second fixation cross, followed by a left- or right-pointing arrow (maximum duration: 2 seconds), to which participants responded as quickly and accurately as possible. In approximately 25% of trials, an auditory stop signal was presented after a variable delay, requiring participants to inhibit their response. The stop-signal delay (SSD) was dynamically adjusted using a staircase procedure (initial delay: 250 ms; ±50 ms based on performance) to index inhibitory control. The inter-trial interval was fixed at 30 seconds.

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• Delay Discounting Task (DDT)

  The study employed a Delay Discounting Task (DDT) to assess individuals' preference for immediate versus delayed rewards. The task included 80 trials, generated by fully crossing four delayed reward amounts (¥25, ¥50, ¥100, ¥500), five delay durations (7, 14, 30, 90, and 180 days), and four discount rates (70%, 85%, 90%, and 95%). Each trial began with a 1.5-second fixation cross, followed by a simultaneous presentation of two options: a smaller immediate reward and a larger delayed reward, with their positions randomized across trials. Participants selected their preferred option using the left or right arrow keys, and no feedback was provided.、

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

Secondary Outcomes (7)

• Hamilton Depression Scale (HAMD-17) score

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• Hamilton Anxiety Scale (HAMA-14) score

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• the score of PANSI

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• The score of Ruminative Responses Scale (RRS)

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

• The score of Difficulties in Emotion Regulation Scale-Short Form (DERS-16)

  Assessments were conducted at baseline (pre-treatment) and on day 1 post-treatment.

Study Arms (3)

Combined Stimulation Group

EXPERIMENTAL

deliver 15 minutes taVNS and 20 minutes of 10hz tACS intervention

Device: 25Hz、300us transcutaneous auricular vagus nerve stimulation and10hz transcranial alternating current stimulation

tACS-Only Group

ACTIVE COMPARATOR

deliver sham 15 minutes taVNS and 20 minutes of 10hz tACS intervention

Device: sham 25Hz、300us transcutaneous auricular vagus nerve stimulation and 10hz transcranial alternating current stimulation

taVNS-Only Group

PLACEBO COMPARATOR

deliver 15 minutes taVNS and 20 minutes of sham 10hz tACS sham intervention ，but 10 Hz active sham control the current will be ramped up to 2 mA and then ramped down to 0 mA within the first 30 seconds.

Device: active 25Hz、300us transcutaneous auricular vagus nerve stimulation and sham10hz transcranial alternating current stimulation

Interventions

25Hz、300us transcutaneous auricular vagus nerve stimulation and10hz transcranial alternating current stimulation DEVICE

The active taVNS stimulation was applied to the cymba conchae, an area exclusively innervated by the auricular branch of the vagus nerve. Active taVNS stimulation protocol was set as follows: pulse width of 300 μs, frequency of 25 Hz, and current intensity adjusted based on each participant's individual threshold, set at 80% of the sensory threshold. The stimulation duration was 15 minutes. Active 10hz transcranial alternating current stimulation: 10 Hz tACS delivered through a 4×1-ring high-definition electrode montage centered on left DLPFC (F3), 2 mA peak-to-peak, 100 % intensity, gradually ramped up over 30 s, maintained for 20 min, then ramped down over 30 s; two sessions per day with at least 4 h between sessions, repeated for 7 consecutive days (14 total sessions).

Combined Stimulation Group

sham 25Hz、300us transcutaneous auricular vagus nerve stimulation and 10hz transcranial alternating current stimulation DEVICE

The sham taVNS stimulation was placed on the earlobe. The two procedures were indistinguishable in terms of appearance, ensuring effective blinding. The stimulation duration was 15 minutes. Active 10HZ transcranial alternating current stimulation: 10 Hz tACS delivered through a 4×1-ring high-definition electrode montage centered on left DLPFC (F3), 2 mA peak-to-peak, 100 % intensity, gradually ramped up over 30 s, maintained for 20 min, then ramped down over 30 s; two sessions per day with at least 4 h between sessions, repeated for 7 consecutive days (14 total sessions).

tACS-Only Group

active 25Hz、300us transcutaneous auricular vagus nerve stimulation and sham10hz transcranial alternating current stimulation DEVICE

The active taVNS stimulation was applied to the cymba conchae, an area exclusively innervated by the auricular branch of the vagus nerve. active taVNS stimulation protocol was set as follows: pulse width of 300 μs, frequency of 25 Hz, and current intensity adjusted based on each participant's individual threshold, set at 80% of the sensory threshold. The stimulation duration was 15 minutes. Sham 10HZ transcranial alternating current stimulation: identical 4×1-ring high-definition electrode montage centered on left DLPFC (F3), 2 mA peak-to-peak current ramped up over 30 s and immediately ramped down to 0 mA, followed by 19.5 min of no stimulation to match the 20-min session duration of active tACS; delivered twice daily (≥4 h apart) for 7 consecutive days (14 total sessions).

taVNS-Only Group

Eligibility Criteria

• Age: 12 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Meet the proposed diagnostic criteria for non-suicidal self-injury (NSSI) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with ≥5 documented self-injury episodes and at least one incident within the past month as assessed by the Adolescent Non-Suicidal Self-Injury Assessment Questionnaire (ANSAQ)
• Aged 12-18 years
• Right-handed
• Possess formal education experience sufficient to comprehend experimental protocols
• Normal or corrected-to-normal binocular visual acuity
• Voluntarily participate with legal guardians providing written informed consent

You may not qualify if:

• Montreal Cognitive Assessment (MoCA) score \< 26
• History of suicide attempts
• History of epilepsy, brain surgery, tumors, or clinically significant head trauma
• History of substance abuse or severe physical diseases
• Received physical or psychological interventions within the past three months

Sponsors & Collaborators

• Anhui Medical University: lead

Study Sites (1)

School of Mental Health and Psychological Sciences

Hefei, Anhui, China

RECRUITING

MeSH Terms

Conditions

Self-Injurious Behavior

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Hongyan Zhu

  School of Mental Health and Psychological Sciences, Anhui Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongyan Zhu

CONTACT

＋ 86 18155313002; 2445011125@stu.ahmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Graduate Student Researcher

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: March 23, 2026
• Study Start: October 16, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

CN (1)