Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder and Generalized Anxiety Disorder

Официальное название

A Double-Blind, Randomized, Sham-Controlled Clinical Trial of Temporal Interference Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder and Generalized Anxiety Disorder

Обзор

This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD). All participants will be enrolled as two independent cohorts and randomized separately within each diagnostic group. Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. Participants with generalized anxiety disorder will be randomized to receive high-frequency TI-tACS(80Hz), low-frequency TI-tACS(5Hz), or sham stimulation targeting the right amygdala. The intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months. The primary outcome for the MDD cohort is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. The primary outcome for the GAD cohort is the change from baseline in the Hamilton Anxiety Rating Scale (HAMA) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles in both the MDD and GAD cohorts.

Подробное описание

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent psychiatric disorders associated with substantial disability and impaired quality of life. Neuroimaging studies have demonstrated abnormalities in distributed cortical-subcortical circuits, particularly involving the amygdala, which plays a central role in emotional processing and symptom regulation. Although several neuromodulation techniques have shown therapeutic potential, currently available approaches have limited ability to selectively modulate deep brain structures without invasive procedures.

Temporal interference transcranial alternating current stimulation (TI-tACS) is a novel non-invasive neuromodulation technique that delivers two high-frequency alternating currents with slightly different frequencies to generate a low-frequency envelope within deep brain regions. This approach enables selective modulation of deep neural structures, such as the amygdala, while minimizing stimulation of the overlying cortex.

This is a multicenter, randomized, triple-blind, sham-controlled clinical trial designed to evaluate the efficacy, safety, and neurobiological mechanisms of TI-tACS in participants with MDD or GAD. Participants with either disorders will be enrolled as independent cohorts and randomized separately within each diagnostic group to receive active or sham TI-tACS according to the study protocol.

Approximately 192 participants (102 with MDD and 90 with GAD) will be recruited. Following written informed consent, participants will undergo baseline assessments and subsequent study evaluations according to the protocol. Study assessments include clinical evaluations, neurocognitive testing, electroencephalography (EEG), magnetic resonance imaging (MRI), and biological sample collection. TI-tACS treatment consists of 20 stimulation sessions administered over two weeks (two sessions per day for five consecutive days, followed by a two-day break, and another five consecutive treatment days).

Participants will also complete scheduled post-treatment follow-up assessments to evaluate the persistence of treatment effects and the long-term safety of TI-tACS.

Вмешательства

• Устройство Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)
  Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) is a non-invasive neuromodulation technique that generates a low-frequency envelope field in deep brain regions, particularly the right amygdala, through the interaction of two high-frequency currents. In the MDD cohort, low-frequency stimulation will be delivered at 2 Hz and high-frequency stimulation at 130 Hz. In the GAD cohort, low-frequency stimulation will be delivered at 5 Hz and high-frequency stimulation at 80
• Устройство Sham Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)
  Sham Temporal Interference transcranial Alternating Current Stimulation will mimic the sensory experience of active stimulation without delivering effective current.

Первичные конечные точки

• Change from baseline in the Hamilton Depression Rating Scale(HAMD-17) scores at week 2 for MDD participants. Change from baseline in the Hamilton Anxiety Rating Scale(HAMA) scores at week 2 for GAD participants. [Срок оценки: 2 weeks(from baseline)]

Вторичные конечные точки (12)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score for Participants With Major Depressive Disorder [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Adverse Events Related to treatment [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Intolerance of Uncertainty Scale (IUS) Score in Participants With Generalized Anxiety Disorder [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Penn State Worry Questionnaire (PSWQ) Score in Participants With Generalized Anxiety Disorder [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Patient Health Questionnaire-9 (PHQ-9) [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in the Hamilton Anxiety Rating Scale (HAMA) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Young Mania Rating Scale (YMRS) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Pittsburgh Sleep Quality Index (PSQI) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Beck Scale for Suicide Ideation (BSI) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• hange in 10-item Connor-Davidson Resilience Scale (CD-RISC-10) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in Chinese Version of the Cognitive Emotion Regulation Questionnaire (CERQ-C) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]
• Change in State Anxiety Inventory (S-AI) Score [Срок оценки: Baseline to month 2 follow-up(post treatment)]

Критерии участия

Критерии включения

• Age between 18 and 55 years (inclusive), any gender;
• Diagnosis of a single or recurrent episode of Major Depressive Disorder (MDD) or Generalized Anxiety Disorder (GAD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features;
• For MDD participants: HAMD-17 score ≥14; inadequate response to stable, regular antidepressant medication for at least 1 month at an adequate dose;
• For GAD participants: HAMA score ≥14; stable, regular medication for at least 2 months;
• Education level: junior high school or above; adequate cognitive and language ability to understand and complete study assessments;
• Voluntary participation with signed informed consent; ability to comply with study visits, treatment schedules, laboratory tests, and other study procedures.

Критерии исключения

• History of psychiatric disorders other than MDD or GAD;
• Pregnancy or lactation;
• Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma);
• History of significant head injury or coma
• Receipt of physical therapies such as electroconvulsive therapy or rTMS within the past six months before enrollment
• Suspected or confirmed history of alcohol or substance dependence;
• Current severe suicidal ideation or recent suicide attempt;
• Current participation in another clinical trial or recent use of prohibited psychotropic medications;
• Positive urine drug screening or abnormal thyroid function tests;
• Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG);
• Inability to provide fully informed consent.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07712159 · LYG20240121

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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