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生酮饮食与神经调控在治疗抵抗性抑郁症中的应用 (ALIGN)

2026年8月4日 更新者：Dr. Sean Michael Nestor、Sunnybrook Health Sciences Centre

辅助性低碳生酮饮食增强影像引导神经调控治疗难治性抑郁症

本临床试验的目的是测试在患有难治性抑郁症的成人中，将生酮饮食（KD）与个性化加速间歇性θ波刺激（iTBS）相结合，是否比iTBS与标准健康饮食相结合能更显著地减轻抑郁症状。该试验还旨在确定参与者是否能在加速iTBS治疗过程中可行地遵循生酮饮食，以及该饮食是否会导致酮体水平发生可测量的变化。

具体而言，本研究旨在确定联合干预是否：

  1. 减轻抑郁症状
  2. 增加循环酮体水平
  3. 在加速iTBS治疗期间可行且耐受

参与者将开始进行KD或符合加拿大食品指南的饮食（CFGD），并有一个为期3周的饮食导入期，之后在继续指定饮食的同时接受个性化加速iTBS治疗。在iTBS治疗前后，参与者将完成临床评估，提供血液样本进行代谢测试，并接受MRI扫描以评估大脑连接性。在整个15周的饮食干预期间，将每日测量酮体水平。将比较组内和组间差异，以描述临床结果、代谢和大脑功能的变化。

研究概览

地位

尚未招聘

条件

干预/治疗

研究类型

介入性

注册 (估计的)

60

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 加拿大
    • Ontario
      • Toronto、Ontario、加拿大、M4N 3M5
        • Sunnybrook Health Sciences Centre
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

纳入标准：

  • 年龄18-65岁，不限性别、性别认同、种族和社会经济地位
  • 当前正经历由DSM-5-TR标准定义并经研究医师确认的重度抑郁发作
  • 表现出至少中度症状严重程度（MADRS ≥ 20）
  • 符合难治性抑郁症（TRD）标准，定义为对至少两次充分抗抑郁治疗无反应
  • 未接受过神经调节治疗（无既往rTMS或电休克治疗史）
  • 能够提供知情同意
  • 可参与为期15周的干预，并愿意遵循生酮饮食或加拿大食品指南饮食

排除标准：

  • 存在妨碍参与研究的医学/精神共病，或抑郁症并非主要精神症状
  • 有癫痫、中风或重大神经系统疾病史，过去6个月内出现精神病或物质依赖
  • 存在妨碍参与的身体或认知障碍
  • 女性受试者在研究期间怀孕（自述或血液检查证实）、哺乳或计划怀孕，且BMI < 20 kg/m²
  • 过去12个月内有自杀企图
  • 经研究精神科医生确认存在主动自杀意图
  • 过去12个月内存在活跃的进食障碍
  • 当前正在遵循生酮饮食
  • 过去6个月内习惯性采用低碳水化合物饮食
  • 存在与饮食方案不兼容的胃肠道疾病或食物过敏
  • 酒精摄入量 > 3杯/天或 > 14杯/周
  • 使用抗惊厥药（允许使用剂量 < 2劳拉西泮当量的苯二氮䓬类药物）、GABA激动剂或降低TMS疗效的药物
  • 患有严重躯体疾病
  • 存在MRI禁忌症
  • 不愿进行每日指尖采血检测

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：单身的

武器和干预

参与者组/臂
干预/治疗
实验性的：Ketogenic Diet
Participants in this arm will follow a well-formulated ketogenic diet (low carbohydrate, moderate protein, high fat) for a 3-week dietary lead-in period prior to neuromodulation, and will continue the diet for a total of 12 weeks. The diet is designed to achieve and maintain nutritional ketosis (blood ketone levels of 0.5 to 3 mmol/L). Dietitian support will be provided through scheduled counseling and ongoing monitoring of finger-stick ketone and glucose testing.
设备：Accelerated Intermittent Theta Burst Stimulation (iTBS)
Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is a non-invasive brain stimulation technique approved by the FDA and Health Canada for the treatment of TRD. In this study, participants will receive an accelerated course of imaging-guided, neuronavigated left dorsolateral prefrontal cortex (DLPFC) iTBS targeted based on functional connectivity with the subgenual anterior cingulate cortex (sgACC). Stimulation protocol consists of 1800 pulses per session, delivered at 110% of resting motor threshold, with 50-minute inter-session intervals, for 8 sessions per day over 5 consecutive days.
其他名称：
  • 重复经颅磁刺激 (rTMS)
行为的：Ketogenic Diet
A well-formulated ketogenic diet consisting of low carbohydrate, moderate protein, and high fat intake, designed to achieve and maintain nutritional ketosis (blood ketone levels of 0.5 to 3 mmol/L). Delivered with dietitian-led counseling and monitored via finger-stick ketone and glucose testing.
有源比较器：Canadian Food Guide-Aligned Diet
Participants in this arm will follow a Canadian Food Guide-aligned diet for a 3-week dietary lead-in period prior to neuromodulation and will continue the diet for a total of 12 weeks. The diet will emphasize balanced intake of vegetables, fruits, whole grains, and protein foods, without specific macronutrient restrictions. Dietitian counseling will be approximately matched in frequency and duration to the ketogenic diet arm. Nutritional monitoring will include dietary logs and metabolic assessments without targeted induction of ketosis. Participants will perform finger-stick glucose testing.
设备：Accelerated Intermittent Theta Burst Stimulation (iTBS)
Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is a non-invasive brain stimulation technique approved by the FDA and Health Canada for the treatment of TRD. In this study, participants will receive an accelerated course of imaging-guided, neuronavigated left dorsolateral prefrontal cortex (DLPFC) iTBS targeted based on functional connectivity with the subgenual anterior cingulate cortex (sgACC). Stimulation protocol consists of 1800 pulses per session, delivered at 110% of resting motor threshold, with 50-minute inter-session intervals, for 8 sessions per day over 5 consecutive days.
其他名称：
  • 重复经颅磁刺激 (rTMS)
行为的：Canadian Food Guide-Aligned Diet
A Canadian Food Guide-aligned diet emphasizing balanced intake of vegetables, fruits, whole grains, and protein foods, without specific macronutrient restrictions. Delivered with dietitian counseling matched in frequency and duration to the ketogenic diet arm, and monitored via dietary logs, metabolic assessments, and finger-stick glucose testing.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change in Depression Score on the Montgomery-Asberg Depression Rating Scale (MADRS)
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Change in depression symptomatology as assessed by the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS). Higher scores indicate worse outcomes (greater severity of depressive symptoms)
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Changes in Ketone Levels
大体时间：Baseline through week 12
Change in β-hydroxybutyrate concentrations over the treatment period relative to baseline. β-hydroxybutyrate will be measured daily via finger-stick ketone testing during the lead-in and iTBS phases, and a minimum of three times per week during the post-iTBS dietary continuation phase. Longitudinal change will be analyzed across the treatment period.
Baseline through week 12
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
大体时间：Baseline through week 12
Frequency, severity, and relatedness of adverse events and clinically significant laboratory abnormalities, and discontinuations due to adverse effects, with specific attention to KD-related effects (e.g., hypoglycemia, dehydration, electrolyte disturbances, gastrointestinal symptoms, dyslipidemia) and mood destabilization/suicidality.
Baseline through week 12

次要结果测量

结果测量
措施说明
大体时间
治疗期望
大体时间：基线
治疗期望将使用斯坦福治疗期望量表（SETS）进行评估，该量表在基线时进行，以评估参与者在干预前的期望。 SETS得分越高，表明治疗期望越积极。
基线
Changes in ¹H-MRS Neurochemical Metabolites
大体时间：Baseline to Week 8 (post-iTBS)
Proton magnetic resonance spectroscopy will quantify changes in metabolites associated with neuroplasticity and metabolic function. Metabolite concentrations will be compared from baseline to post-treatment to determine whether nutritional ketosis enhances neurochemical responses to iTBS.
Baseline to Week 8 (post-iTBS)
Changes in Resting-State Functional Connectivity
大体时间：Baseline to Week 8 (post-iTBS)
Resting-state fMRI will be used to assess changes in intrinsic functional connectivity within fronto-cingulate and fronto-striatal networks.
Baseline to Week 8 (post-iTBS)
Changes in Task-Evoked Brain Activation
大体时间：Baseline to Week 8 (post-iTBS)
Task-based fMRI will be used to measure changes in activation within predefined mood-regulation circuits. Contrast maps from an emotional processing task will be compared from baseline to post-treatment to assess neural circuit engagement associated with iTBS combined with dietary intervention.
Baseline to Week 8 (post-iTBS)
Change in Secondary Depression Scores
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Baseline grid-version of the 17-item Hamilton Depression Rating Scale (HDRS) score. The HDRS is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range is 0 to 52, with higher score indicating more severe depression.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Change in Self-Reported Depressive Symptoms
大体时间：Baseline, Week 3 (pre-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS), Week 10 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Self-reported depressive symptom severity will be assessed using the PHQ-9 with changes measured from baseline to each assessment point through the end of treatment. Higher scores on the PHQ-9 represent greater depressive severity.
Baseline, Week 3 (pre-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS), Week 10 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Functional Disability
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Functional disability will be measured using the WHODAS 2.0, with changes evaluated from baseline to the end of treatment. Higher WHODAS scores indicate greater impairment.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Well-being
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Well-being will be evaluated using the WHO-5 Well-Being Index, measured from baseline to the end of treatment. Higher WHO-5 scores represent better well-being.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Change in Anxiety Measure
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
Anxiety symptom severity will be assessed using the Generalized Anxiety Disorder-7 (GAD-7), with improvement examined from baseline to the end of treatment. Higher GAD-7 scores reflect more severe anxiety
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS), Week 26 (post-iTBS), Week 52 (post-iTBS)
BMI (Anthropometric Outcomes)
大体时间：Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
Anthropometric outcomes, including BMI, will be recorded to evaluate changes in adiposity and fat distribution from baseline to the end of treatment.
Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
Waist-to-Hip Ratio (Anthropometric Outcomes)
大体时间：Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
Anthropometric outcomes, including waist circumference and waist-to-hip ratio, will be recorded to evaluate changes in adiposity and fat distribution from baseline to the end of treatment. Higher waist-to-hip ratios indicate greater central adiposity.
Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
NIH Toolbox Dimensional Change Card Sort Test (Executive Functioning)
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Executive functioning will be assessed using the NIH Toolbox Dimensional Change Card Sort Test, with changes evaluated from baseline to the end of treatment. Higher scores reflect better cognitive performance.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
NIH Flanker Inhibitory Control and Attention Test (Executive Functioning)
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Executive functioning will be assessed using the NIH Flanker Inhibitory Control and Attention Test, with changes evaluated from baseline to the end of treatment. Higher scores reflect better cognitive performance.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Working Memory
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Working memory will be measured using the NIH Toolbox List Sorting Working Memory Test, with changes compared from baseline to post-treatment. Higher scores indicate stronger working memory ability.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Episodic Memory
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Episodic memory will be assessed using the NIH Toolbox Auditory Verbal Learning Test and the Picture Sequence Memory Test, with changes evaluated from baseline to the end of treatment. Higher scores indicate better episodic memory performance.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Waist-to-Hip Ratio (Anthropometric outcome)
大体时间：Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
Anthropometric outcomes, including waist circumference and waist-to-hip ratio, will be recorded to evaluate changes in adiposity and fat distribution from baseline to the end of treatment. Higher waist-to-hip ratios indicate greater central adiposity.
Baseline, Day 5 (post-iTBS), Week 5 (post-iTBS), Week 8 (post-iTBS)
NIH Toolbox Oral Symbol Digit Test (Processing Speed)
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Processing speed will be evaluated using the NIH Toolbox Oral Symbol Digit Test, with changes assessed from baseline to post-treatment. Higher scores reflect faster processing speed.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
NIH Toolbox Pattern Comparison Processing Speed Test (Processing Speed)
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Processing speed will be evaluated using the NIH Toolbox Pattern Comparison Processing Speed Test, with changes assessed from baseline to post-treatment. Higher scores reflect faster processing speed.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Perceived Physical Capacity
大体时间：Baseline, Days 1-5 of iTBS treatment, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
The modified Rating of Perceived Exertion (RPE) scale will be used to assess participants' perceived physical effort and tolerance during routine physical activities and daily tasks. This subjective measure captures how hard the body feels it is working based on internal sensations such as breathing, cardiovascular strain, muscle fatigue, and overall exertion, providing an index of perceived functional capacity for physical activity.
Baseline, Days 1-5 of iTBS treatment, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Objective Physical Capacity
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Objective indices of physical capacity and fatigue will be obtained using handgrip dynamometry. Maximal voluntary force (MVF) will be measured as the average of three maximal-effort trials, reflecting peak isometric grip strength and overall neuromuscular capacity of the hand and forearm muscles.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Fatigue
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Time to exhaustion (TTE) during a sustained submaximal grip task will be used to quantify fatigue resistance and endurance, defined as the duration for which participants can maintain a prescribed grip force before they are unable to sustain the target level.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Change in HbA1c Levels
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in fasting HbA1c (measured in mmol/mol) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Fasting Glucose Levels
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in fasting glucose (measured in mmol/L) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Lipid Profile
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in lipid profile (total cholesterol, LDL, HDL, triglycerides; measured in mmol/mol) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Liver Function Panel
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in liver function (ALT, AST, ALP; measured in U/L) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Total Protein and Albumin
大体时间：Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Changes in total protein and albumin (measured in g/L) across the study period.
Baseline, Week 5 (post-iTBS), Week 8 (post-iTBS), Week 12 (post-iTBS)
Change in Total Bilirubin
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in total bilirubin (measured in mg/dL) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Electrolytes
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in electrolytes (measured in mmol/L) across the study period
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in Urea and Calcium
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in urea and calcium (measured in mg/dL) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in BDNF
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in BDNF (measured in ng/mL) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in IL-6 and TNF-alpha Levels
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in inflammatory markers (measured in pg/mL) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Change in CRP Levels
大体时间：Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)
Changes in CRP (measured in mg/L) across the study period.
Baseline, Day 1 of iTBS, Week 5 (post-iTBS), Week 8 (post-iTBS)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Sunnybrook Health Sciences Centre

合作者

Baszucki Group

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年8月1日

初级完成 (估计的)

2028年1月1日

研究完成 (估计的)

2028年1月1日

研究注册日期

首次提交

2026年1月21日

首先提交符合 QC 标准的

2026年1月21日

首次发布 (实际的)

2026年1月29日

研究记录更新

最后更新发布 (实际的)

2026年8月7日

上次提交的符合 QC 标准的更新

2026年8月4日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 6944

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

去标识化的个体参与者数据（IPD）及相关支持文件（包括研究方案、统计分析计划和数据字典）将被共享，以支持二次研究。 数据将共享给合格的研究人员，用于科学合理的分析，前提是需根据桑尼布鲁克研究所的政策批准并签署数据使用协议。 访问请求将经过审核，以确保科学价值、可行性及参与者保密性的保护。

IPD 共享时间框架

研究方案和知情同意书将在研究启动前发布。 试验结果将在研究完成后尽快公布。 去标识化个体参与者数据（IPD）将在主要结果发布后12个月（或研究完成后12个月，若无发表）开始提供。

IPD 共享访问标准

共享数据将包括去标识化的个体参与者数据（IPD）和支持文件（研究方案、统计分析计划和数据字典）。

访问权限将仅限于具有适当机构隶属关系、获得伦理批准并提交方法学合理方案的研究人员。请求将由研究首席研究员（或指定的数据访问委员会）审核。

获批用户将通过安全、经机构批准的数据共享系统获取访问权限。所有用户必须签署数据使用协议，禁止重新识别、二次共享以及超出批准方案范围外的任何使用。

IPD 共享支持信息类型

  • 研究方案
  • 树液
  • 国际碳纤维联合会
  • 企业社会责任

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

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