Pilot Study on the Effects of Intensified Repetitive Transcranial Magnetic Stimulation on Immunological Blood Parameters in Patients With Depression and Comorbid Post-COVID-19 Condition
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Total score change in the Becks Depression Inventory, version 2 (BDI-II, self-rating)
研究概览
简要总结
This is a monocentric, randomized pilot study conducted at the Max Planck Institute of Psychiatry, Munich. The study investigates the effects of two different intermittent theta-burst stimulation (iTBS) schedules on biological and clinical outcomes in patients with depression and comorbid Post-COVID-19 condition (PCC). Participants will be randomized into two arms, both receiving a total of 30 active iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) at 90% resting motor threshold using a PowerMAG 100 ppTMS stimulator:
- Standard Arm: One iTBS session per day, five days per week, over six weeks.
- Intensified Arm: Six iTBS sessions per day, approximately one-hour apart, over five consecutive days.
The primary outcomes are changes in immunological blood markers (C-reactive protein [CRP], tumor necrosis factor [TNF], interleukin-1β [IL-1β], interleukin-6 [IL-6]) and depressive symptomatology measured by Beck Depression Inventory-II (BDI-II) and Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes include fatigue (Fatigue Severity Scale [FSS], Fatigue Scale for Motor and Cognitive Functions [FSMC], Post-Exertional Malaise questionnaire [PEM]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), functioning (Sheehan Disability Scale [SDS]), anxiety (Beck Anxiety Inventory [BAI]) and an exploratory adverse effect screening. Follow-up assessments will be performed three days after treatment completion and again at three months post-intervention to evaluate both short- and medium-term effects. Biospecimen collection will include approximately 141 ml of peripheral blood per participant across three time points (baseline, post-treatment, +3 days). Samples will be analyzed for inflammatory markers and securely stored in the institutional biobank of the Max Planck Institute of Psychiatry in accordance with data protection and ethical guidelines. Safety and tolerability will be continuously monitored, including documentation of adverse events. The results of this pilot study are expected to provide preliminary evidence on whether accelerated iTBS protocols may exert differential effects on neuroinflammatory processes and depressive symptomatology in patients with Post-COVID-19 condition, thereby informing larger controlled clinical trials.
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
- None
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 years
- •Capacity to consent (legally competent, written informed consent including data protection)
- •Diagnosis of depression (at least moderate severity, BDI-II ≥ 20), including major depressive episode in bipolar disorder
- •Comorbid diagnosis of Post-COVID-19 condition (WHO definition)
- •Insufficient improvement of depressive symptoms under psychopharmacological treatment
- •Stable psychopharmacological medication for at least 4 weeks prior to start of iTBS
排除标准
- •Age <18 years or >65 years
- •Pregnancy, planned pregnancy, or breastfeeding
- •Legal guardianship or cognitive impairment preventing valid informed consent
- •Severe developmental disorder or intellectual disability
- •Acute or chronic substance abuse (alcohol, prescription drugs, or illicit drugs)
- •Current treatment with benzodiazepines or Z-substances
- •Acute suicidality
- •Psychotic symptoms
- •Severe neurological disorder (e.g., major brain injury, neurodegenerative disease)
- •Ongoing treatment with another neurostimulation method (ECT, TMS, VNS)
- •Contraindications to TMS, including: Intracranial metal, implants, shunts, Cochlear implant, pacemaker, implantable defibrillator, History of seizures or epileptiform EEG
- •Severe general medical illness (e.g., anemia requiring transfusion, severe arrhythmias, cardiomyopathy)
研究组 & 干预措施
Standard iTBS (once daily)
Standard: Participants receive one iTBS session per day, Monday through Friday, for 6 weeks (total 30 sessions). Each session consists of intermittent theta-burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC) at 90% of resting motor threshold using a PowerMAG 100 ppTMS stimulator. Each session lasts approximately 3 minutes.
干预措施: Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS (Device)
Intensified iTBS (6x daily)
Intensified: Participants receive six iTBS sessions per day at intervals of about 60 minutes, for 5 consecutive days (total 30 sessions). Each session uses the same iTBS parameters as in the standard arm: stimulation of the left dorsolateral prefrontal cortex (DLPFC) at 90% of resting motor threshold with a PowerMAG 100 ppTMS stimulator, lasting about 3 minutes per session.
干预措施: Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS (Device)
结局指标
主要结局
Total score change in the Becks Depression Inventory, version 2 (BDI-II, self-rating)
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion
Change in depression symptomatology, comparison between two arms. Range of the test is 0-63, a higher score indicates a worse condition.
Total score change in the clinician-rated Montgomery Asberg Depression scale (MADRS)
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion
Change in depression symptomatology, comparison between two arms. Overall score range 0-60, a higher score indicates a more severe depression.
Change in immunophenotypic marker CRP from baseline to post-treatment
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment
Differences in CRP from baseline to post-treatment between intensified iTBS and standard iTBS in inflammatory markers (based on material extracted from peripheral blood)
Change in immunophenotypic marker TNF from baseline to post-treatment
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment
Differences in TNF from baseline to post-treatment between intensified iTBS and standard iTBS in inflammatory markers (based on material extracted from peripheral blood)
Change in immunophenotypic marker IL-1ß from baseline to post-treatment
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment
Differences in IL-1ß from baseline to post-treatment between intensified iTBS and standard iTBS in inflammatory markers (based on material extracted from peripheral blood)
Change in immunophenotypic marker IL-6 from baseline to post-treatment
时间窗: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment
Differences in IL-6 from baseline to post-treatment between intensified iTBS and standard iTBS in inflammatory markers (based on material extracted from peripheral blood)
次要结局
- Change in Fatigue Scale for Motor and Cognitive Functions (FSMC, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Pittsburgh Sleep Quality Index (PSQI, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Epworth Sleepiness Scale (ESS, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Beck Anxiety Inventory (BAI, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Sheehan Disability Scale (SDS, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Fatigue Severity Scale (FSS, self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Change in Post-Exertional Malaise (PEM) Questionnaire (self-rating)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)
- Adverse Event Screening (Exploratory)(baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion)