Transcranial Alternating Current Stimulation to Enhance Mindfulness Therapy in Generalized Anxiety Disorder

NCT07648797 | Not Yet Recruiting

• 1 other identifier: KYZZ20260020
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, sham-controlled clinical trial will evaluate whether individualized alpha-frequency transcranial alternating current stimulation (tACS) can enhance the effects of mindfulness therapy in adults with generalized anxiety disorder. A total of 99 participants will be randomly assigned to one of three groups: synchronous tACS combined with mindfulness therapy, desynchronous tACS combined with mindfulness therapy, or sham tACS combined with mindfulness therapy. All participants will receive a standardized mindfulness therapy program. The study will compare changes in anxiety symptoms, worry, mindfulness, attention control, cognitive performance, and neurophysiological measures across the three groups. Assessments will be conducted from baseline through follow-up visits to examine both clinical effects and possible neural mechanisms.

Conditions

Generalized Anxiety Disorder (GAD)

Keywords

Transcranial Alternating Current Stimulation; tACS; Mindfulness Therapy; Mindfulness Meditation; Individualized Alpha Frequency; Frontoparietal Network; Dorsolateral Prefrontal Cortex; Inferior Parietal Lobule; Worry; Executive Attention

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Hamilton Anxiety Rating Scale total score at Week 2 post-randomization

  The Hamilton Anxiety Rating Scale (HAMA) is a clinician-administered scale used to assess the severity of anxiety symptoms. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms. This outcome is defined as the change in HAMA total score from baseline to Week 2 post-randomization, calculated as the Week 2 score minus the baseline score. A greater reduction indicates greater improvement in anxiety symptoms.

  Baseline and Week 2

Secondary Outcomes (6)

• Change in Generalized Anxiety Disorder-7 Score From Baseline to Follow-up

  Baseline, Week 1, Week 2, Month 1, Month 2, Month 4, and Month 6

• Change in Penn State Worry Questionnaire Score From Baseline to Follow-up

  Baseline, Week 1, Week 2, Month 1, Month 2, Month 4, and Month 6

• Change in Five Facet Mindfulness Questionnaire Score From Baseline to Follow-up

  Baseline, Week 1, Week 2, Month 1, Month 2, Month 4, and Month 6

• Change in Attentional Control Scale Score From Baseline to Follow-up

  Baseline, Week 1, Week 2, Month 1, Month 2, Month 4, and Month 6

• tACS-Related Adverse Effects Assessed by the tACS Adverse Effects Questionnaire

  Week 1 and Week 2

Study Arms (3)

Synchronous tACS Plus Mindfulness Therapy

EXPERIMENTAL

Participants in this arm will receive individualized alpha-frequency transcranial alternating current stimulation (tACS) combined with standardized mindfulness therapy. The stimulation electrodes will be placed over F3 and P3, corresponding to the left dorsolateral prefrontal cortex and left inferior parietal lobule, and will deliver in-phase stimulation. Mindfulness therapy will be delivered using the same standardized program as in the other arms.

Device: Synchronous Individualized Alpha-Frequency tACS; Behavioral: Mindfulness Therapy

Desynchronous tACS Plus Mindfulness Therapy

ACTIVE COMPARATOR

Participants in this arm will receive individualized alpha-frequency tACS combined with the same standardized mindfulness therapy program. The stimulation targets, treatment duration, and general stimulation setup will be the same as in the synchronous tACS arm, but the phase difference between the F3 and P3 stimulation electrodes will be set at 180 degrees.

Device: Desynchronous Individualized Alpha-Frequency tACS; Behavioral: Mindfulness Therapy

Sham tACS Plus Mindfulness Therapy

SHAM COMPARATOR

Participants in this arm will receive sham tACS combined with the same standardized mindfulness therapy program. Sham stimulation will include 30-second ramp-up and ramp-down periods at the beginning and end of stimulation to mimic the sensation of active tACS. No active current will be delivered during the main 20-minute stimulation period, while the electrodes will remain in place to maintain blinding.

Device: Sham tACS; Behavioral: Mindfulness Therapy

Interventions

Synchronous Individualized Alpha-Frequency tACS DEVICE

Individualized alpha-frequency transcranial alternating current stimulation (tACS) will be delivered to the frontoparietal network. Stimulation electrodes will be placed over F3 and P3, corresponding to the left dorsolateral prefrontal cortex and left inferior parietal lobule. In the synchronous tACS condition, the F3 and P3 stimulation electrodes will deliver in-phase sinusoidal alternating current. The stimulation frequency will be individualized based on each participant's alpha-band phase locking value peak between F3 and P3.

Also known as: Synchronous tACS, In-Phase tACS, Transcranial Alternating Current Stimulation

Synchronous tACS Plus Mindfulness Therapy

Desynchronous Individualized Alpha-Frequency tACS DEVICE

Individualized alpha-frequency tACS will be delivered using the same stimulation targets and general setup as the synchronous tACS condition. Stimulation electrodes will be placed over F3 and P3, corresponding to the left dorsolateral prefrontal cortex and left inferior parietal lobule. In the desynchronous tACS condition, the phase difference between the F3 and P3 stimulation electrodes will be set at 180 degrees.

Also known as: Desynchronous tACS, Anti-Phase tACS, 180-Degree Phase Difference tACS

Desynchronous tACS Plus Mindfulness Therapy

Sham tACS DEVICE

Sham tACS will be delivered with the electrodes placed in the same positions as in the active tACS conditions. The sham condition will include 30-second ramp-up and ramp-down periods at the beginning and end of stimulation to mimic the sensation of active stimulation. No active current will be delivered during the main 20-minute stimulation period, while the electrodes will remain in place to maintain blinding.

Also known as: Sham Transcranial Alternating Current Stimulation

Sham tACS Plus Mindfulness Therapy

Mindfulness Therapy BEHAVIORAL

Participants will receive a standardized mindfulness therapy program for 2 weeks, with 10 sessions in total. Each session will last 40 minutes. The program follows a progressive structure of awareness, acceptance, and application. The first five sessions focus on breath awareness and body scan practices. The last five sessions focus on observing anxiety-related bodily sensations and worry-related thoughts with a nonjudgmental and accepting attitude, and on using breathing space practices to redirect attention to the present moment.

Also known as: Mindfulness Meditation Training, Standardized Mindfulness Training

Desynchronous tACS Plus Mindfulness Therapy; Sham tACS Plus Mindfulness Therapy; Synchronous tACS Plus Mindfulness Therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Outpatients or inpatients of The Second Xiangya Hospital of Central South University.
• Diagnosis of generalized anxiety disorder as the primary diagnosis according to the International Classification of Diseases 11th Revision (ICD-11) diagnostic criteria, confirmed by two experienced psychiatrists.
• Hamilton Anxiety Rating Scale (HAMA) total score of 14 or higher.
• Aged 18 to 60 years, inclusive.
• Right-handed.
• Junior high school education or above, with sufficient ability to understand the study procedures, complete informed consent, clinical scales, and cognitive assessments.
• Currently not using anxiolytic or antidepressant medications, or receiving a stable medication regimen for at least 1 month before enrollment, with no planned changes in the medication regimen during the 2-week treatment period unless clinically necessary.
• Voluntarily agrees to participate in the study, signs the informed consent form, and is able to comply with study visits, treatment procedures, laboratory examinations, and other study requirements.

You may not qualify if:

• Presence of psychotic symptoms.
• Meeting ICD-11 diagnostic criteria for schizophrenia or other primary psychotic disorders, bipolar or related disorders, current depressive episode, dysthymic disorder, or post-traumatic stress disorder currently or within the past year.
• Organic brain disease or severe physical illness, including but not limited to thyroid disease, systemic lupus erythematosus, diabetes, severe pulmonary, hepatic, or renal impairment, infection, or major trauma.
• Clinically significant uncorrectable sensory impairment, such as hearing impairment that prevents effective communication.
• Pregnancy or lactation.
• Contraindications to transcranial electrical stimulation or related procedures, including metal implants in the body, intracranial hypertension, skull defects, brain tumor, severe heart disease, unstable vital signs due to serious physical illness, acute cerebrovascular disease, or a history of adverse reactions to electrical stimulation.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for this study.

Sponsors & Collaborators

• Central South University: lead

Study Sites (1)

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

MeSH Terms

Conditions

Generalized Anxiety Disorder

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Yan Zhang, PhD

  Second Xiangya Hospital of Central South University

  STUDY CHAIR

• Yumeng Ju, PhD

  Second Xiangya Hospital of Central South University

  STUDY DIRECTOR

Central Study Contacts

Yumeng Ju, PhD

CONTACT

+86-18100731091; yumeng.ju@csu.edu.cn

Fanqi Zhou

CONTACT

+86-18711022278; 2205228535@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors will be masked to group assignment. Sham stimulation will include 30-second ramp-up and ramp-down periods at the beginning and end of stimulation to mimic the sensation of active tACS, while no active current will be delivered during the main 20-minute stimulation period. The psychotherapist, tACS operator, and data collectors will be independent research personnel, and outcome assessors will not be involved in treatment delivery.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Researcher

Model Details: Participants will be randomly assigned in a 1:1:1 ratio to one of three parallel groups: synchronous tACS plus mindfulness therapy, desynchronous tACS plus mindfulness therapy, or sham tACS plus mindfulness therapy. Each participant will receive only the assigned intervention throughout the treatment period. All groups will receive the same standardized mindfulness therapy program, and the groups will differ only in the tACS stimulation condition.

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: June 15, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)