Efficacy and Safety of Transcranial Temporal Interference Stimulation for Depression

Обзор

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.

Подробное описание

Major depressive disorder (MDD) is a common and disabling mental disorder. Although medication, psychotherapy, and established brain stimulation methods can help many people with MDD, some participants still have insufficient improvement. Transcranial temporal interference stimulation (tTIS) is a non-invasive brain stimulation technique that may allow modulation of deeper brain regions or pathways. This study is designed to evaluate whether tTIS can improve depressive symptoms in adults with MDD, assess its safety, and explore potential neuroimaging mechanisms.

This is a single-center, randomized, double-blind, sham-controlled clinical trial conducted at Zhongda Hospital, Southeast University. Eligible participants with MDD will be randomly assigned in a 1:1:1 ratio to one of three groups: active tTIS targeting the left anterior limb of the internal capsule (ALIC), active tTIS targeting the left subgenual anterior cingulate cortex (sgACC), or sham tTIS. The sham stimulation will be designed to provide sensory feedback similar to active stimulation while maintaining blinding.

Participants with MDD will receive 10 treatment sessions over 5 consecutive days, with two 20-minute sessions each day. Clinical symptoms and safety will be assessed at baseline, after treatment, and during follow-up. The main clinical outcome is the change in the 24-item Hamilton Depression Rating Scale (HAMD-24) total score from baseline to after treatment. Secondary outcomes include follow-up changes in depressive symptoms, response and remission rates, anxiety symptoms, anhedonia, psychosomatic symptoms, side effects, and adverse events.

Multimodal 5.0T brain magnetic resonance imaging (MRI) will be collected from participants with MDD before and after treatment. MRI measures will include structural imaging, resting-state functional imaging, and diffusion imaging. These data will be used to explore changes in brain structure, functional connectivity, and diffusion-related measures after tTIS, and to identify potential imaging biomarkers related to treatment response.

Вмешательства

• Устройство Active Transcranial Temporal Interference Stimulation Targeting Left ALIC
  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.
• Устройство Active Transcranial Temporal Interference Stimulation Targeting Left sgACC
  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.
• Устройство Sham Transcranial Temporal Interference Stimulation
  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.

Первичные конечные точки

• Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 1 [Срок оценки: Baseline and Week 1]

Вторичные конечные точки (12)

• Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 2 [Срок оценки: Baseline and Week 2]
• Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 6 [Срок оценки: Baseline and Week 6]
• Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 1 [Срок оценки: Week 1]
• Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 2 [Срок оценки: Week 2]
• Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 6 [Срок оценки: Week 6]
• Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 1 [Срок оценки: Baseline and Week 1]
• Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 2 [Срок оценки: Baseline and Week 2]
• Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 6 [Срок оценки: Baseline and Week 6]
• Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 1 [Срок оценки: Baseline and Week 1]
• Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 2 [Срок оценки: Baseline and Week 2]
• Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 6 [Срок оценки: Baseline and Week 6]
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score From Baseline to Week 1 [Срок оценки: Baseline and Week 1]

Критерии участия

Критерии включения

• Diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), by two independent psychiatrists
• 24-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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongda Hospital Southeast University — Нанкин

Публикации

• 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/ PMID 39268031
• Grossman 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 30264149

Идентификаторы

NCT: NCT07612501 · MR-32-25-078202 · 82271570 · BF2025611

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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