Efficacy and Safety of Transcranial Alternating Current Stimulation (tACS) Combined With Stable Medication in Adolescents With Depression

NCT07185451 | Recruiting DMC

• 1 other identifier: 1stChongqingMU__ZXY
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, sham-controlled pilot study will evaluate the feasibility, acceptability, safety, and preliminary clinical effects of transcranial alternating current stimulation as an adjunctive treatment for adolescents with major depressive disorder. It will also examine changes in depressive symptoms and related clinical outcomes, while exploring potential effects on emotional regulation, cognitive function, and brain function following the intervention.

Conditions

Depression - Major Depressive Disorder

Outcome Measures

Primary Outcomes (5)

• Recruitment Feasibility (Number of Participants Enrolled)

  The total number of participants successfully enrolled in this study will be recorded to assess recruitment feasibility. The goal is to recruit 30 participants (15 in each of the two groups) over a 2-year period.

  From the start of recruitment to completion of enrollment, up to 2 years

• Intervention adherence (number of participants who completed the full 20 treatment sessions)

  This outcome measure will assess participants' adherence to the 20 sessions of transcranial alternating current stimulation. Adherence is defined as completing all 20 sessions. Adherence is calculated by dividing the number of participants who met this criterion by the total number of participants.

  End of treatment at Week 4

• Retention Rate (Number of Participants Remaining at 16-Week Follow-up)

  This outcome measure will assess the proportion of participants still enrolled in the study at the 16-week follow-up assessment. Retention rate is calculated as the number of participants who completed the 16-Week assessment divided by the number of participants enrolled at baseline.

  From randomization through the final follow-up assessment at Week 16

• Response rate and remission rate of depressive symptoms

  Preliminary clinical efficacy will be assessed by change in the Children's Depression Rating Scale-Revised (CDRS-R) total score from baseline. CDRS-R is a clinician-rated scale used to assess the severity of depressive symptoms in children and adolescents. It consists of 17 items, and the total score ranges from 17 to 113. Higher scores indicate more severe depressive symptoms. Changes in CDRS-R total score from baseline will be assessed at the end of treatment and at follow-up visits. Response rate of depressive symptoms will be defined as a ≥50% reduction in CDRS-R total score from baseline, and remission rate of depressive symptoms will be defined as a CDRS-R total score ≤28.

  Baseline, throughout the 4-week treatment period, and during follow-up through Week 16

• Incidence of Adverse Events and Serious Adverse Events

  Adverse events, abbreviated as AEs, and serious adverse events, abbreviated as SAEs, will be assessed to evaluate the safety and tolerability of the intervention. An AE is defined as any unfavorable medical occurrence in a participant during the study period, regardless of whether it is considered related to the intervention. An SAE is defined as any adverse event that results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is otherwise considered medically significant. The number and proportion of participants experiencing at least one AE or SAE will be recorded throughout the study period. The severity, outcome, and relationship to the intervention will also be documented.

  From the first stimulation session through the final follow-up assessment at Week 16

Secondary Outcomes (9)

• Change in BDI-II (Beck Depression Inventory-II) scores from baseline

  Baseline, Week 4, Week 8, and Week 16

• Change in HAMA score from baseline

  Baseline, Week 4, Week 8, and Week 16

• Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline

  Baseline, Week 4, Week 8, and Week 16

• Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale)

  Baseline, Week 4, Week 8, and Week 16

• Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline

  Baseline, Week 4, Week 8, and Week 16

Study Arms (2)

tACS

EXPERIMENTAL

Participants in this group will receive transcranial alternating current stimulation (tACS) in addition to their ongoing stable pharmacotherapy. tACS will be delivered using the NEXALIN ADI device (Beijing Neslin Technology Co., Ltd.) with a frequency of 77.5 Hz and current intensity of 15 mA. One electrode is placed on the forehead and two electrodes on the mastoid processes. Each session lasts approximately 40 minutes, with a total of 20 sessions administered over 4 weeks (5 sessions per week). The intervention aims to modulate cortical activity and improve depressive symptoms, cognitive function, and emotional regulation.

Device: tACS

Sham

SHAM COMPARATOR

Participants in this group will receive sham stimulation in addition to their ongoing stable pharmacotherapy. A sham device identical in appearance, sound, and operation to the active tACS device will be used but will not deliver any electrical current. Treatment is administered in the same schedule as the active group (20 sessions over 4 weeks, 5 sessions per week). Both participants and operators are blinded to the treatment assignment to ensure study integrity.

Device: tACS

Interventions

tACS DEVICE

This intervention uses the NEXALIN ADI alternating current stimulation device from Beijing Naisilin Technology Co., Ltd., to deliver targeted stimulation to the prefrontal cortex and bilateral mastoid regions. The prefrontal cortex electrode directly stimulates the cerebral cortex, while the mastoid electrodes ensure the synchronized activation of bilateral neural pathways. Stimulation is applied at a frequency of 77.5 Hz and a current intensity of 15 mA, aiming to optimize brainwave synchronization and modulate brain activity. Participants will undergo daily sessions lasting approximately 40 minutes each, for a total of 20 sessions over 4 weeks. The non-invasive nature of the intervention, combined with its precise targeting of specific brain regions, distinguishes it from other neuromodulation therapies. The treatment aims to enhance neural synchronization, promote neuroplasticity, and provide a non-pharmacological therapeutic alternative for patients.

tACS

Eligibility Criteria

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

You may qualify if:

• Age 12-18 years.
• Meet DSM-5 diagnostic criteria for a current depressive episode, as confirmed by the K-SADS-PL.
• Children's Depression Rating Scale-Revised (CDRS-R) score ≥40 at baseline.
• Stable psychotropic medication treatment for at least 4 weeks prior to enrollment and willingness to continue the same regimen throughout the study.

You may not qualify if:

• Psychiatric comorbidities other than anxiety disorders.
• Depression with psychotic features.
• Young Mania Rating Scale (YMRS) score \>13.
• History of neurological disorders (e.g., epilepsy, traumatic brain injury) or severe physical illnesses (e.g., thyroid disease, lupus, diabetes, significant liver, kidney, or lung impairment, major trauma).
• Previous treatment with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), tACS, or other neurostimulation therapies.
• Current use of antiepileptic drugs or high-dose benzodiazepines.
• History of alcohol or substance abuse or dependence.
• Pregnant or breastfeeding females.
• Contraindications to MRI.
• Current high suicide risk.

Sponsors & Collaborators

• First Affiliated Hospital of Chongqing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 40000, China

RECRUITING

Related Publications (13)

• Clancy KJ, Andrzejewski JA, You Y, Rosenberg JT, Ding M, Li W. Transcranial stimulation of alpha oscillations up-regulates the default mode network. Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2110868119. doi: 10.1073/pnas.2110868119.

  PMID: 34969856 RESULT

• Jones KT, Johnson EL, Gazzaley A, Zanto TP. Structural and functional network mechanisms of rescuing cognitive control in aging. Neuroimage. 2022 Nov 15;262:119547. doi: 10.1016/j.neuroimage.2022.119547. Epub 2022 Aug 5.

  PMID: 35940423 RESULT

• Yan CG, Chen X, Li L, Castellanos FX, Bai TJ, Bo QJ, Cao J, Chen GM, Chen NX, Chen W, Cheng C, Cheng YQ, Cui XL, Duan J, Fang YR, Gong QY, Guo WB, Hou ZH, Hu L, Kuang L, Li F, Li KM, Li T, Liu YS, Liu ZN, Long YC, Luo QH, Meng HQ, Peng DH, Qiu HT, Qiu J, Shen YD, Shi YS, Wang CY, Wang F, Wang K, Wang L, Wang X, Wang Y, Wu XP, Wu XR, Xie CM, Xie GR, Xie HY, Xie P, Xu XF, Yang H, Yang J, Yao JS, Yao SQ, Yin YY, Yuan YG, Zhang AX, Zhang H, Zhang KR, Zhang L, Zhang ZJ, Zhou RB, Zhou YT, Zhu JJ, Zou CJ, Si TM, Zuo XN, Zhao JP, Zang YF. Reduced default mode network functional connectivity in patients with recurrent major depressive disorder. Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9078-9083. doi: 10.1073/pnas.1900390116. Epub 2019 Apr 12.

  PMID: 30979801 RESULT

• Chai Y, Gehrman P, Yu M, Mao T, Deng Y, Rao J, Shi H, Quan P, Xu J, Zhang X, Lei H, Fang Z, Xu S, Boland E, Goldschmied JR, Barilla H, Goel N, Basner M, Thase ME, Sheline YI, Dinges DF, Detre JA, Zhang X, Rao H. Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation. Proc Natl Acad Sci U S A. 2023 Jun 27;120(26):e2214505120. doi: 10.1073/pnas.2214505120. Epub 2023 Jun 20.

  PMID: 37339227 RESULT

• Wang J, Zhao W, Wang H, Leng H, Xue Q, Peng M, Min B, Jin X, Tan L, Gao K, Wang H. Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder. Gen Psychiatr. 2024 Mar 8;37(2):e101338. doi: 10.1136/gpsych-2023-101338. eCollection 2024.

  PMID: 38476648 RESULT

• Biackova N, Adamova A, Klirova M. Transcranial alternating current stimulation in affecting cognitive impairment in psychiatric disorders: a review. Eur Arch Psychiatry Clin Neurosci. 2024 Jun;274(4):803-826. doi: 10.1007/s00406-023-01687-7. Epub 2023 Sep 8.

  PMID: 37682331 RESULT

• Zhou J, Li D, Ye F, Liu R, Feng Y, Feng Z, Li R, Li X, Liu J, Zhang X, Zhou J, Wang G. Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: A randomized controlled trial. Brain Stimul. 2024 Jul-Aug;17(4):760-768. doi: 10.1016/j.brs.2024.06.004. Epub 2024 Jun 14.

  PMID: 38880208 RESULT

• Elyamany O, Leicht G, Herrmann CS, Mulert C. Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. Eur Arch Psychiatry Clin Neurosci. 2021 Feb;271(1):135-156. doi: 10.1007/s00406-020-01209-9. Epub 2020 Nov 19.

  PMID: 33211157 RESULT

• Bowes L, Joinson C, Wolke D, Lewis G. Peer victimisation during adolescence and its impact on depression in early adulthood: prospective cohort study in the United Kingdom. Br J Sports Med. 2016 Feb;50(3):176-83. doi: 10.1136/bjsports-2015-h2469rep.

  PMID: 26782765 RESULT

• Consoli A, Peyre H, Speranza M, Hassler C, Falissard B, Touchette E, Cohen D, Moro MR, Revah-Levy A. Suicidal behaviors in depressed adolescents: role of perceived relationships in the family. Child Adolesc Psychiatry Ment Health. 2013 Mar 16;7(1):8. doi: 10.1186/1753-2000-7-8.

  PMID: 23497551 RESULT

• Hankin BL. Depression from childhood through adolescence: Risk mechanisms across multiple systems and levels of analysis. Curr Opin Psychol. 2015 Aug;4:13-20. doi: 10.1016/j.copsyc.2015.01.003.

  PMID: 25692174 RESULT

• Barker MM, Beresford B, Bland M, Fraser LK. Prevalence and Incidence of Anxiety and Depression Among Children, Adolescents, and Young Adults With Life-Limiting Conditions: A Systematic Review and Meta-analysis. JAMA Pediatr. 2019 Sep 1;173(9):835-844. doi: 10.1001/jamapediatrics.2019.1712.

  PMID: 31282938 RESULT

• Beardslee WR, Brent DA, Weersing VR, Clarke GN, Porta G, Hollon SD, Gladstone TR, Gallop R, Lynch FL, Iyengar S, DeBar L, Garber J. Prevention of depression in at-risk adolescents: longer-term effects. JAMA Psychiatry. 2013 Nov;70(11):1161-70. doi: 10.1001/jamapsychiatry.2013.295.

  PMID: 24005242 RESULT

Central Study Contacts

Xinyu Zhou

CONTACT

15823996993; zhouxinyu@cqmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: This study uses a parallel assignment design. Participants will be randomly allocated in a 1:1 ratio to either the active tACS group or the sham stimulation group. Both groups will continue stable pharmacotherapy throughout the study. The intervention group will receive 20 sessions of active tACS over 4 weeks, while the control group will receive sham stimulation with an identical device that delivers no current. Participants remain in their assigned group for the entire duration of the study without crossover.

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 22, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: August 17, 2026

Record last verified: 2026-08

Locations

CN (1)