Efficacy and Safety of Transcranial Temporal Interference Stimulation for Depression
3 other identifiers
interventional
60
1 country
1
Brief Summary
The goal of this clinical trial is to learn whether transcranial temporal interference stimulation (tTIS) can help treat major depressive disorder (MDD) in adults. The study will also learn about the safety of tTIS and explore how it may affect brain structure and brain function. The main questions it aims to answer are whether active tTIS lowers depression symptom scores more than sham stimulation after treatment, and what medical problems or side effects participants have during or after tTIS. Researchers will compare active tTIS targeting the left anterior limb of the internal capsule, active tTIS targeting the left subgenual anterior cingulate cortex, and sham stimulation. Sham stimulation is designed to feel similar to real stimulation but does not provide the same active treatment. Participants with MDD will be randomly assigned to one of the three groups. They will receive two 20-minute treatment sessions each day for 5 days. They will complete depression, anxiety, pleasure, psychosomatic symptom, and safety assessments before treatment, after treatment, and during follow-up. They will also have brain magnetic resonance imaging scans before and after treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started May 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2026
CompletedFirst Posted
Study publicly available on registry
May 28, 2026
CompletedStudy Start
First participant enrolled
May 30, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 30, 2027
May 28, 2026
May 1, 2026
1 year
May 20, 2026
May 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 1
The 24-item Hamilton Depression Rating Scale (HAMD-24) will be used to assess the severity of depressive symptoms. The total score ranges from 0 to 76, with higher scores indicating more severe depressive symptoms. The primary outcome is the change in HAMD-24 total score from baseline to Week 1.
Baseline and Week 1
Secondary Outcomes (18)
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 2
Baseline and Week 2
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 6
Baseline and Week 6
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 1
Week 1
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 2
Week 2
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 6
Week 6
- +13 more secondary outcomes
Other Outcomes (3)
Change in Brain Structural Imaging Metrics From 5.0T Magnetic Resonance Imaging
Baseline and Day 6
Change in Resting-state Functional Connectivity From 5.0T Functional Magnetic Resonance Imaging
Baseline and Day 6
Change in Diffusion Imaging Metrics From 5.0T Magnetic Resonance Imaging
Baseline and Day 6
Study Arms (3)
Active tTIS Targeting Left ALIC
ACTIVE COMPARATORParticipants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left anterior limb of the internal capsule (ALIC). Treatment will be delivered twice daily for 5 consecutive days, with each session lasting 20 minutes and a 30-minute interval between sessions.
Active tTIS Targeting Left sgACC
ACTIVE COMPARATORParticipants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left subgenual anterior cingulate cortex (sgACC). Treatment will be delivered twice daily for 5 consecutive days, with each session lasting 20 minutes and a 30-minute interval between sessions.
Sham tTIS
SHAM COMPARATORParticipants in this arm will receive sham transcranial temporal interference stimulation (tTIS). Sham stimulation will be delivered using the same type of device and will provide sensory feedback similar to active stimulation, but it will not provide the same active treatment dose. Treatment sessions will follow the same schedule as the active stimulation arms.
Interventions
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left anterior limb of the internal capsule (ALIC). The stimulation target will be individualized based on each participant's magnetic resonance imaging data. The difference frequency will be 130 Hz. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left subgenual anterior cingulate cortex (sgACC). The stimulation target will be individualized based on each participant's magnetic resonance imaging data. The difference frequency will be 130 Hz. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Participants in this arm will receive sham transcranial temporal interference stimulation (tTIS) using the same type of device as active stimulation. Sham stimulation will provide sensory feedback similar to active stimulation to help maintain masking, but it will not deliver the same active treatment dose. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Eligibility Criteria
You may qualify if:
- Diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), by two independent psychiatrists
- item Hamilton Depression Rating Scale (HAMD-24) total score greater than 20 at baseline
- Aged 18 to 65 years
- Right-handed
- Able to understand the study procedures and willing to provide written informed consent
You may not qualify if:
- History of epilepsy, brain tumor, or brain trauma
- Receipt of transcranial magnetic stimulation, transcranial electrical stimulation, or electroconvulsive therapy within the past 3 months
- Presence of metal implants or other contraindications to transcranial electrical stimulation or magnetic resonance imaging
- Acute or severe suicidal ideation
- Any other condition judged by the investigators to make participation unsuitable for this study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yonggui Yuanlead
Study Sites (1)
Zhongda Hospital Southeast University
Nanjing, Jiangsu, 210009, China
Related Publications (2)
Demchenko I, Rampersad S, Datta A, Horn A, Churchill NW, Kennedy SH, Krishnan S, Rueda A, Schweizer TA, Griffiths JD, Boyden ES, Santarnecchi E, Bhat V. Target engagement of the subgenual anterior cingulate cortex with transcranial temporal interference stimulation in major depressive disorder: a protocol for a randomized sham-controlled trial. Front Neurosci. 2024 Aug 29;18:1390250. doi: 10.3389/fnins.2024.1390250. eCollection 2024.
PMID: 39268031RESULTGrossman N, Okun MS, Boyden ES. Translating Temporal Interference Brain Stimulation to Treat Neurological and Psychiatric Conditions. JAMA Neurol. 2018 Nov 1;75(11):1307-1308. doi: 10.1001/jamaneurol.2018.2760. No abstract available.
PMID: 30264149RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yonggui Yuan, PhD
Zhongda Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
- Masking Details
- Participants, treatment operators, and outcome assessors will be masked to group allocation. Eligible participants with major depressive disorder will be randomly assigned to active tTIS targeting the left anterior limb of the internal capsule, active tTIS targeting the left subgenual anterior cingulate cortex, or sham tTIS according to a computer-generated randomization table. Active and sham stimulation will be delivered using the same type of device, and sham stimulation will be designed to provide sensory feedback similar to active stimulation. Clinical outcome assessments will be performed by trained assessors who are not involved in treatment delivery and are unaware of the assigned intervention.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Chief Physician
Study Record Dates
First Submitted
May 20, 2026
First Posted
May 28, 2026
Study Start
May 30, 2026
Primary Completion (Estimated)
May 30, 2027
Study Completion (Estimated)
May 30, 2027
Last Updated
May 28, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share
Individual participant data will not be publicly shared because the study involves sensitive mental health information and neuroimaging data. Data sharing may increase the risk of participant identification. De-identified data may be made available from the principal investigator upon reasonable request and with approval from the ethics committee, when permitted by applicable regulations and the informed consent.