One-Day cTBS Over the Precuneus (OcTOPUS)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 4
研究概览
简要总结
The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain.
The main questions this study aims to answer are:
- Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
- Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive.
Participants will:
- Complete screening procedures and baseline assessments of depression, rumination, and cognitive function
- Receive 20 sessions of active or sham TMS during one in-person study day
- Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention
- Report any side effects or medical problems experienced during the study
Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.
详细描述
Treatment-resistant depression may involve dysfunction across distributed brain networks rather than a disturbance confined to a single brain region. The precuneus is a posterior hub of the default mode network and is involved in internally directed and self-referential processing. Altered interactions among the default mode, affective, and cognitive control networks have been implicated in depressive symptoms and rumination. In this study, precuneus continuous theta-burst stimulation (cTBS) is conceptualized as a hypothesis-driven network intervention that may modulate precuneus-centered network interactions implicated in depression.
A double-cone coil will be used to increase electric-field penetration toward the medial posteromedial cortex beneath the Pz scalp location of the international 10-20 electroencephalography system. Intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is included as an additional active treatment arm because this region is an established stimulation target for depression treatment. The three-arm design allows the novel precuneus target and the established left dorsolateral prefrontal cortex target to be evaluated within the same accelerated treatment framework and compared with sham stimulation.
Participants will be assigned to the three initial study groups using the minimal sufficient balance (MSB) randomization method, with sex and baseline depression severity, as measured by the Montgomery-Åsberg Depression Rating Scale, used as balancing factors. The target allocation ratio for the randomized, sham-controlled phase will be 1:1:1. Group allocation will be concealed from participants. Each active or sham intervention will consist of 20 stimulation sessions administered during a single day, with session onsets separated by approximately 30 minutes.
The primary efficacy analyses will use a longitudinal mixed-model framework to estimate treatment effects and evaluate the two prespecified active-versus-sham comparisons. The familywise type I error rate will be controlled across these two comparisons. The direct comparison between precuneus cTBS and left dorsolateral prefrontal cortex iTBS will be considered exploratory.
After completing the 4-week follow-up period, participants initially assigned to sham stimulation may elect to enter an open-label active TMS extension. Extension participants will be assigned to precuneus cTBS or left dorsolateral prefrontal cortex iTBS using the MSB method, with a target allocation ratio of 1:1. Sex and depression severity at the end of the sham-controlled phase, as measured by the Week 4 Montgomery-Åsberg Depression Rating Scale score, will be used as balancing factors. Because only a subset of participants assigned to sham stimulation is expected to enter the extension, extension analyses will be considered exploratory and hypothesis-generating.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Participants are masked to treatment assignment during the randomized, sham-controlled phase. The Principal Investigator, who administers TMS and conducts clinical outcome assessments, is not masked to treatment assignment. The designated study team member responsible for randomization is also not masked. Other study personnel, including study physicians, are not informed of treatment assignment during the randomized phase. Masking does not apply to the optional open-label extension.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •Able to speak, read, and understand English sufficiently to complete the study assessments and provide informed consent independently.
- •Diagnosis of major depressive disorder according to DSM-5-TR criteria, confirmed by a qualified physician.
- •Treatment-resistant depression, defined as an inadequate response to at least two adequate trials of antidepressant pharmacotherapy.
- •Patient Health Questionnaire-9 (PHQ-9) total score of 10 or higher.
排除标准
- •Any condition identified through TMS safety screening that, in the judgment of a study physician, presents an unacceptable safety risk for TMS. Such conditions may include:
- •A history of a serious adverse reaction during TMS treatment.
- •A history of seizure.
- •A history of stroke.
- •A history of serious head injury or neurosurgery.
- •Metal in the head outside the mouth, such as shrapnel, surgical clips, or metal fragments.
- •An implanted device, such as a cardiac pacemaker, cochlear implant, medical pump, or intracardiac line.
- •Frequent or severe headaches.
- •Another brain-related condition or an illness that caused brain injury.
- •A family history of epilepsy.
- •Permanent tattoos on the head or neck.
- •Current recreational drug use.
- •Current pregnancy or possible pregnancy.
- •Use of a medication or combination of medications, a recent medication change, or medication withdrawal that, in the judgment of a study physician, presents an unacceptable safety risk, including a clinically significant increase in seizure risk.
- •Current or lifetime diagnosis of bipolar I disorder, bipolar II disorder, a schizophrenia spectrum disorder, or another primary psychotic disorder.
- •Active suicidal ideation with intent or plan requiring immediate clinical intervention, or another acute safety concern that cannot be safely managed within the study.
研究组 & 干预措施
Precuneus cTBS
Participants receive 20 sessions of active continuous theta-burst stimulation (cTBS) targeting the Pz location of the international 10-20 EEG system during a single day. Stimulation is delivered using a double-cone coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 40 seconds, for a total of 12,000 pulses. Session onsets are separated by approximately 30 minutes. If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
干预措施: Precuneus-targeted continuous theta-burst stimulation (Device)
Left dlPFC iTBS
Participants receive 20 sessions of active intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex during a single day. The target is identified using the Beam F3 method, and stimulation is delivered using a figure-of-eight coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 3 minutes, for a total of 12,000 pulses. Session onsets are separated by approximately 30 minutes. If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.
干预措施: Left dorsolateral prefrontal cortex intermittent theta-burst stimulation (Device)
Sham TMS
Participants receive 20 sessions of sham TMS at the left dorsolateral prefrontal cortex location identified using the Beam F3 method during a single day. A figure-of-eight coil is inverted so that the active surface faces away from the scalp. The device is operated at 80% of the participant's resting motor threshold, and sham stimulation follows the same stimulation pattern and approximate 3-minute duration as active iTBS. Session onsets are separated by approximately 30 minutes. After completing the Week 4 assessment, participants may enter an optional open-label extension and are randomized to receive active precuneus cTBS or left dlPFC iTBS.
干预措施: Sham transcranial magnetic stimulation (Device)
结局指标
主要结局
Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 4
时间窗: Baseline and 1, 2, 3, and 4 weeks after the intervention
The MADRS is a clinician-administered 10-item scale used to assess the severity of depressive symptoms. Each item is scored from 0 to 6, yielding a total score ranging from 0 to 60. Higher scores indicate greater depressive symptom severity. MADRS total scores will be assessed at baseline and at Weeks 1, 2, 3, and 4 after the intervention. Post-intervention scores will be compared between treatment groups with adjustment for baseline MADRS total score. The primary treatment comparison will be conducted at Week 4.
次要结局
- 17-Item Hamilton Depression Rating Scale (HAM-D-17) Total Score Through Week 4(Baseline and 1, 2, 3, and 4 weeks after the intervention)
- Patient Health Questionnaire-9 (PHQ-9) Total Score Through Week 4(Baseline and 1, 2, 3, and 4 weeks after the intervention)
- Ruminative Responses Scale (RRS) Total Score Through Week 4(Baseline and 1, 2, 3, and 4 weeks after the intervention)
- Montreal Cognitive Assessment (MoCA) Total Score at Week 4(Baseline and 4 weeks after the intervention)
- MGH/McLean Objective Neurocognitive Assessment (MONA) Total Score at Week 4(Baseline and 4 weeks after the intervention)
研究者
Hakjoo Kim
Postdoctoral Research Fellow
Mclean Hospital