Demchenko Ilya, Rampersad Sumientra, Datta Abhishek, Horn Andreas, Churchill Nathan W, Kennedy Sidney H, Krishnan Sridhar, Rueda Alice, Schweizer Tom A, Griffiths John D, Boyden Edward S, Santarnecchi Emiliano, Bhat Venkat
Interventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, Toronto, ON, Canada.
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Front Neurosci. 2024 Aug 29;18:1390250. doi: 10.3389/fnins.2024.1390250. eCollection 2024.
Transcranial temporal interference stimulation (tTIS) is a new, emerging neurostimulation technology that utilizes two or more electric fields at specific frequencies to modulate the oscillations of neurons at a desired spatial location in the brain. The physics of tTIS offers the advantage of modulating deep brain structures in a non-invasive fashion and with minimal stimulation of the overlying cortex outside of a selected target. As such, tTIS can be effectively employed in the context of therapeutics for the psychiatric disease of disrupted brain connectivity, such as major depressive disorder (MDD). The subgenual anterior cingulate cortex (sgACC), a key brain center that regulates human emotions and influences negative emotional states, is a plausible target for tTIS in MDD based on reports of its successful neuromodulation with invasive deep brain stimulation.
This pilot, single-site, double-blind, randomized, sham-controlled interventional clinical trial will be conducted at St. Michael's Hospital Unity Health Toronto in Toronto, ON, Canada. The primary objective is to demonstrate target engagement of the sgACC with 130 Hz tTIS using resting-state magnetic resonance imaging (MRI) techniques. The secondary objective is to estimate the therapeutic potential of tTIS for MDD by evaluating the change in clinical characteristics of participants and electrophysiological outcomes and providing feasibility and tolerability estimates for a large-scale efficacy trial. Thirty participants (18-65 years) with unipolar, non-psychotic MDD will be recruited and randomized to receive 10 sessions of 130 Hz tTIS or sham stimulation ( = 15 per arm). The trial includes a pre- vs. post-treatment 3T MRI scan of the brain, clinical evaluation, and electroencephalography (EEG) acquisition at rest and during the auditory mismatch negativity (MMN) paradigm.
This study is one of the first-ever clinical trials among patients with psychiatric disorders examining the therapeutic potential of repetitive tTIS and its neurobiological mechanisms. Data obtained from this trial will be used to optimize the tTIS approach and design a large-scale efficacy trial. Research in this area has the potential to provide a novel treatment option for individuals with MDD and circuitry-related disorders and may contribute to the process of obtaining regulatory approval for therapeutic applications of tTIS.
ClinicalTrials.gov, identifier NCT05295888.
经颅颞叶干扰刺激（tTIS）是一种新兴的神经刺激技术，它利用两个或更多特定频率的电场来调节大脑中所需空间位置的神经元振荡。tTIS的物理学原理具有以非侵入性方式调节深部脑结构的优势，并且对选定靶点之外的上层皮质刺激最小。因此，tTIS可有效地应用于治疗大脑连接中断的精神疾病，如重度抑郁症（MDD）。膝下前扣带回皮质（sgACC）是调节人类情绪并影响负面情绪状态的关键脑区，基于其通过侵入性深部脑刺激成功进行神经调节的报道，它是tTIS治疗MDD的一个合理靶点。
这项试点、单中心、双盲、随机、假对照干预性临床试验将在加拿大多伦多市圣迈克尔医院联合健康中心进行。主要目标是使用静息态磁共振成像（MRI）技术证明130Hz的tTIS对sgACC的靶点参与情况。次要目标是通过评估参与者临床特征和电生理结果的变化，并为大规模疗效试验提供可行性和耐受性估计，来评估tTIS对MDD的治疗潜力。将招募30名（18 - 65岁）单相、非精神病性MDD患者，并随机分为接受10次130Hz的tTIS或假刺激（每组15人）。该试验包括治疗前与治疗后的脑部3T MRI扫描、临床评估以及静息状态和听觉失配负波（MMN）范式期间的脑电图（EEG）采集。
本研究是针对精神疾病患者检验重复tTIS治疗潜力及其神经生物学机制的首批临床试验之一。从该试验获得的数据将用于优化tTIS方法并设计大规模疗效试验。该领域的研究有可能为MDD和与神经回路相关疾病的患者提供一种新的治疗选择，并可能有助于tTIS治疗应用获得监管批准的进程。
ClinicalTrials.gov，标识符NCT05295888。
