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

NCT07197138 | Recruiting

• 1 other identifier: 25-0648
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depressive Disorder; Post-Acute COVID-19 Syndrome

Keywords

Major depressive disorder; Post-COVID-19-condition; neuropsychology; psychometry; Immunemarkers; IL-6; TNF; CRP; repetitive transcranial magnetic stimulation; intermittent theta burst; accelerated rTMS; neuroinflammation

Outcome Measures

Primary Outcomes (6)

• Change in immunophenotypic marker CRP from baseline to post-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)

  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

  Differences in TNF from baseline to post-treatment between intensified iTBS and standard iTBS in inflammatory markers (based on material extracted from peripheral blood)

  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

  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)

  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

  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)

  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)

  Change in depression symptomatology, comparison between two arms. Range of the test is 0-63, a higher score indicates a worse condition.

  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)

  Change in depression symptomatology, comparison between two arms. Overall score range 0-60, a higher score indicates a more severe depression.

  baseline (day of first treatment), day of 15th treatment, 3 days after 30th (last) treatment, follow-up 3 months after treatment completion

Secondary Outcomes (8)

• 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 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 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

• 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

Study Arms (2)

Standard iTBS (once daily)

ACTIVE COMPARATOR

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.

Device: Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS

Intensified iTBS (6x daily)

EXPERIMENTAL

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.

Device: Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS

Interventions

Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS DEVICE

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.

Intensified iTBS (6x daily); Standard iTBS (once daily)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Max-Planck-Institute of Psychiatry: lead

Study Sites (1)

Max-Planck-Institute of Psychiatry

Munich, Bavaria, 80804, Germany

RECRUITING

MeSH Terms

Conditions

Depressive Disorder; Post-Acute COVID-19 Syndrome; Depressive Disorder, Major; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Diseases; Inflammation

Study Officials

• Angelika Erhardt-Lehmann, MD, Prof.

  Max-Planck-Institute of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandros Balaskas, MD

CONTACT

0049-089-30622-1402; Ambulanz@psych.mpg.de

Angelika Erhardt-Lehmann, MD, Prof.

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two active iTBS schedules: once-daily for 6 weeks vs six times daily for 5 days; total 30 sessions per participant.

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: September 29, 2025
• Study Start: September 11, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

DE (1)