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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Change in immunophenotypic marker CRP from baseline to post-treatment — 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 — 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 — 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 — 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)
• Total score change in the Becks Depression Inventory, version 2 (BDI-II, 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 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) — 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.

Trial sites (1)

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