Brain Oscillation-synchronized Stimulation of the Frontal Cortex in Major Depressive Disorder

NCT06345651 | Unknown

• 1 other identifier: 2023-03, Version 7
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is a common severe psychiatric disease with enormous socioeconomic costs for the patient and society alike. Current pharmacological treatments are ineffective in a substantial fraction of patients and are accompanied by unwanted side effects. Using a novel non-invasive brain stimulation method to specifically target and modulate dysfunctional brain oscillations with high spatial and temporal precision this study will investigate the efficacy of EEG-triggered transcranial magnetic stimulation to alleviate de-pressive symptomatology in patients with MDD in a double-blind randomized controlled pilot clinical trial.

Conditions

Major Depressive Disorder

Keywords

Noninvasive Brain Stimulation; Transcranial magnetic stimulation; TMS; Personalized Medicine; Closed-Loop; Brain Oscillation; Depression; TBS

Outcome Measures

Primary Outcomes (1)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  The Montgomery-Åsberg Depression Rating Scale (MADRS) is a questionnaire for external assessment of the severity of a depressive syndrome. The questionnaire consists of 10 questions. The questions are rated on a 7-point scale from 0 to 6. The total score ranges from 0 (best outcome) to 60 (worst outcome) points by summing up. The questionnaire is considered gold standard in the assessment of depressive symptoms. It will be performed at baseline and at the end of the treatment.

  baseline, immediately after the intervention

Secondary Outcomes (6)

• MADRS (Montgomery-Åsberg Depression Rating Scale) 4 weeks after intervention

  4 weeks after the last interventional session

• HDRS-17 (Hamilton Depression Rating Scale-17)

  baseline, immediately after the intervention

• BDI-2 (Beck Depression Inventory-2)

  baseline, immediately after the intervention

• IDS-30 (Inventory of depressive symptoms-30)

  baseline, immediately after the intervention

• Response Rate

  immediately after the intervention

Study Arms (2)

Theta negative peak triggered TMS of left dmPFC

EXPERIMENTAL

Repetitive TMS (100 Hz triple pulses) of the dmPFC will be applied daily for four weeks (5 sessions per week on working days, 20 sessions in total). Stimulation triggers will be brain oscillation-synchronized based on EEG extracted over left dmPFC, synchronized with the negative peak of endogenous theta oscillations in left dmPFC.

Device: Transcranial Magnetic Stimulation

iTBS TMS of left dlPFC

ACTIVE COMPARATOR

Standard intermittent Theta Burst Stimulation of the dlPFC will be applied daily for four weeks (5 sessions per week on working days, 20 sessions in total). Stimulation triggers will be applied independently of the EEG signal.

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

Individually MR-neuronavigated TMS, 600 pulses, 120% RMT

Theta negative peak triggered TMS of left dmPFC; iTBS TMS of left dlPFC

Eligibility Criteria

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

You may qualify if:

• Subjects have to be 18 to 65 years old
• Subjects meet DSM-5 criteria for current major depressive disorder (MDD), confirmed with the Structured Clinical Interview for DSM-5.
• Subjects score 20 points or more on the Montgomery-Åsberg Depression Rating Scale (MADRS).
• Subjects must have had at least one non-response (meaning a failure to achieve remission) in a previous pharmacological antidepressant treatment trial of sufficient (meaning a doses considered to be effective (e.g., superior to placebo in controlled clinical trials) and the duration needs to be sufficient to produce a ro-bust therapeutic effect (e.g., 12 weeks)) dosage and duration as assessed by the ATHF; treatment failure can be for the current or any prior depressive episode; medication resistance for the current episode is not required.
• Subject is in good physical and mental health. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
• Subject is willing to comply with the study restrictions.

You may not qualify if:

• Subject is under the age of legal consent.
• Subject has a diagnosis of bipolar disorder.
• Subject suffers from current symptoms of psychosis.
• Subject has active suicidal ideation with plan and/or intent.
• A current major depressive episode longer than 5 years.
• Subject has a history of substance abuse or dependence within the past 2 years.
• Subject has a diagnosis of antisocial or borderline personality disorder.
• Subject suffers from other major psychiatric or medical comorbidity
• Subject has a history of seizure disorder
• Subject has a history of severe head injury with loss of consciousness.
• Subject had a prior brain surgery
• Subjects with intake of pro-convulsive medication, e.g. imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, MDMA (ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline, in accord with present consensus guidelines on safety, ethical considerations, and application of TMS in clinical practice and research.
• Daily intake of Benzodiazepines other than Lorazepam \>1 mg/d
• Subject has a cardiac pacemaker, implanted medication pump, intracardiac line, or acute, unstable cardiac disease.
• Subject has an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head (excluding the mouth) that cannot be safely removed.

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Related Publications (1)

• Lieb A, Zrenner B, Becker-Sadzio J, Gordon PC, Kozak G, Zrenner C, Martus P, Ziemann U, Fallgatter A. Brain oscillation-synchronized stimulation for major depression: a randomized controlled trial comparing EEG-triggered repetitive TMS with standard iTBS (Acronym: BOSSFRONT2). Eur Arch Psychiatry Clin Neurosci. 2026 Jan 21. doi: 10.1007/s00406-025-02176-9. Online ahead of print. No abstract available.

  PMID: 41563436 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Ulf Ziemann, Prof.

  University Hospital Tuebingen

  STUDY DIRECTOR

• Andreas J Fallgatter, Prof.

  University Hospital Tuebingen

  STUDY DIRECTOR

Central Study Contacts

Anne Lieb, Dr.

CONTACT

+4970712980483; anne.lieb@uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In both conditions the identical setup is used consisting of Neuronavigation, EEG and TMS. Only in the experimental condition the treatment will be EEG-informed. In the control condition the treatment will be applied indepentently of the EEG signal.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a single-site randomized standard TMS therapy-controlled double-blind paral-lel-group design clinical trial.

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: April 3, 2024
• Study Start: September 1, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: April 3, 2024

Record last verified: 2024-01

Locations

DE (1)