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

NCT ID: NCT07197138

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-11
• Study Completion Date: 2027-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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)

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Max-Planck-Institute of Psychiatry

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angelika Erhardt-Lehmann, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Max-Planck-Institute of Psychiatry

Locations

Max-Planck-Institute of Psychiatry

Munich, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Alexandros Balaskas, MD

Role: CONTACT

Ambulanz@psych.mpg.de

0049-089-30622-1402

Angelika Erhardt-Lehmann, MD, Prof.

Role: CONTACT

Facility Contacts

Reception Outpatient Clinic

Role: primary

Ambulanz@psych.mpg.de

0049-089-30622-1402

Other Identifiers

25-0648

Identifier Type: -

Identifier Source: org_study_id