Adjunctive Low-carb Ketogenic Diet to Enhance Imaging-guided Neuromodulation in Treatment Resistant Depression
概览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Depression Score on the Montgomery-Asberg Depression Rating Scale (MADRS)
概览
简要总结
The goal of this clinical trial is to test whether combining a ketogenic diet (KD) with personalized, accelerated intermittent theta burst stimulation (iTBS) produces greater reductions in depressive symptoms than iTBS combined with a standard healthy diet in adults with treatment-resistant depression. The trial also aims to determine whether participants can feasibly follow a ketogenic diet during an accelerated iTBS treatment course and whether the diet produces measurable changes in ketone levels.
Specifically, the study aims to determine whether the combined intervention:
- Reduces depressive symptoms
- Increases circulating ketone levels
- Is feasible and tolerable during accelerated iTBS treatment
Participants will begin either a KD or a Canadian Food Guide-aligned diet (CFGD) with a 3-week dietary lead-in period, after which they will undergo a course of personalized, accelerated iTBS while continuing their assigned diet. Before and after the iTBS treatment course, participants will complete clinical assessments, provide blood samples for metabolic testing, and undergo MRI scans to assess brain connectivity. Ketone levels will be measured daily throughout the 12-week dietary intervention. Within-group and between-group differences will be compared to characterize changes in clinical outcomes, metabolism, and brain functioning.
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 of any sex, gender identity, ethnicity and socioeconomic status
- •Currently experiencing a major depressive episode as defined by DSM-5-TR criteria and confirmed by a study physician
- •Presenting with at least moderate symptom severity (MADRS ≥ 20)
- •Meeting criteria for treatment-resistant depression (TRD), defined as non-response to at least two adequate antidepressant trials
- •Neuromodulation-naïve (no past rTMS or electroconvulsive therapy)
- •Able to provide informed consent
- •Available for the 15-week intervention and willing to follow either a ketogenic or Canadian Food Guide-aligned diet
排除标准
- •Medical/psychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern
- •History of epilepsy, stroke, or major neurological conditions, psychosis, or substance dependence within the last 6 months
- •Physical or cognitive disability interfering with participation
- •Females who are pregnant (self-report or via blood work), nursing, or planning a pregnancy during the timespan of the study BMI \< 20 kg/m²
- •Suicide attempts in the past 12 months
- •Active suicidal intent as confirmed by study psychiatrist
- •Active eating disorder in the past 12 months
- •Currently following a KD
- •Habitual low-carb diet in the past 6 months
- •GI disorders or food allergies incompatible with dietary protocols
研究组 & 干预措施
Ketogenic Diet
Participants in this arm will begin 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 using daily finger-stick ketone and glucose testing.
干预措施: Accelerated Intermittent Theta Burst Stimulation (iTBS) (Device)
Canadian Food Guide-Aligned Diet
Participants in this arm will begin 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 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 daily finger-stick glucose testing.
干预措施: Accelerated Intermittent Theta Burst Stimulation (iTBS) (Device)
结局指标
主要结局
Change in Depression Score on the Montgomery-Asberg Depression Rating Scale (MADRS)
时间窗: Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS)
Change in depression symptomatology as assessed by the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) (range 0-60). Higher scores indicate worse outcomes (greater severity of depressive symptoms)
Changes in Ketone Levels
时间窗: Baseline through week 12
Change in fasting morning β-hydroxybutyrate concentrations over the treatment period relative to baseline. Fasting β-hydroxybutyrate will be measured daily via finger-stick ketone testing, and longitudinal change will be analyzed across the treatment period.
Safety and Tolerability
时间窗: 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.
次要结局
- Changes in ¹H-MRS Neurochemical Metabolites(Baseline to Week 4 (post-iTBS))
- Changes in Resting-State Functional Connectivity(Baseline to Week 4 (post-iTBS))
- Changes in Task-Evoked Brain Activation(Baseline to Week 4 (post-iTBS))
- Changes in Metabolic Biomarkers(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Change in Secondary Depression Scores(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Change in Self-Reported Depressive Symptoms(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Functional Disability(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Well-being(Baseline, Day (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Change in Anxiety Measure(Baseline, Day (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Anthropometric Outcomes(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Physiological Measures(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Executive Functioning(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Working Memory(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Episodic Memory(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Processing Speed(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Treatment Expectancy(Baseline)
- Perceived Physical Capacity(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Objective Physical Capacity(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
- Fatigue(Baseline, Day 5 (post-iTBS), Week 4 (post-iTBS), Week 8 (post-iTBS))
研究者
Dr. Sean Michael Nestor
Psychiatrist
Sunnybrook Health Sciences Centre