IMPACT-D+: Immune-Modulating and Psychometric Effects of Accelerated TMS in Depression Plus Comorbid Post-COVID-19 Condition

Официальное название

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

Обзор

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.

Вмешательства

• Устройство Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS
  iTBS at 90% resting motor threshold; bursts of 3 pulses at 50 Hz repeated at 5 Hz; \~3 minutes per session; applied to left dorsolateral prefrontal cortex; 30 total sessions; schedule per arm as specified.

Первичные конечные точки

• Change in immunophenotypic marker CRP from baseline to post-treatment [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment]
• Change in immunophenotypic marker TNF from baseline to post-treatment [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment]
• Change in immunophenotypic marker IL-1ß from baseline to post-treatment [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment]
• Change in immunophenotypic marker IL-6 from baseline to post-treatment [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment]
• Total score change in the Becks Depression Inventory, version 2 (BDI-II, self-rating) [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion]
• Total score change in the clinician-rated Montgomery Asberg Depression scale (MADRS) [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion]

Вторичные конечные точки (8)

• Change in Fatigue Severity Scale (FSS, self-rating) [Срок оценки: 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 Scale for Motor and Cognitive Functions (FSMC, self-rating) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 1 центр

• Max-Planck-Institute of Psychiatry — Munich

Идентификаторы

NCT: NCT07197138 · 25-0648

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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