NCT04392947

Brief Summary

This is a randomized, double-blind, sham-controlled multicenter clinical trial. The aim is to provide evidence for efficacy of TBS in the treatment of patients with major depression. There will be a direct comparison between combined cTBS/iTBS with sham TBS. Overall, 236 patients with major depression will be randomized either to active TBS or sham TBS in a 1:1 ratio. The planned stimulation paradigms will be applied as add-on therapy to standard therapy (antidepressive medication and / or psychotherapy). Patients will receive 30 stimulation sessions in a 6-week treatment period (one session daily from Monday to Friday). Follow up assessments are scheduled 1 and 3 months after end of treatment period.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
238

participants targeted

Target at P75+ for not_applicable major-depressive-disorder

Timeline
Completed

Started Sep 2020

Longer than P75 for not_applicable major-depressive-disorder

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 8, 2020

Completed
11 days until next milestone

First Posted

Study publicly available on registry

May 19, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

September 29, 2020

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2025

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2025

Completed
Last Updated

September 17, 2025

Status Verified

October 1, 2024

Enrollment Period

4.7 years

First QC Date

May 8, 2020

Last Update Submit

September 11, 2025

Conditions

Major Depressive Disorder

Keywords

major depressiontheta burst stimulationdorsolateral prefrontal cortexrandomizedsham-controlledmulticenter

Outcome Measures

Primary Outcomes (1)

  • Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)

    MADRS reduction of at least 50% of baseline value after end of treatment period between active combined iTBS / cTBS and the sham condition. (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)

    6 weeks

Secondary Outcomes (11)

  • Remission rate after treatment

    6 weeks

  • Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)

    6 weeks

  • Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)

    6 weeks

  • Reduction of raw score: Clinical Global Impression (CGI)

    6 weeks

  • Reduction of raw score: Beck Depression Inventory (BDI-II)

    10 and 18 weeks

  • +6 more secondary outcomes

Study Arms (2)

combined iTBS/cTBS

ACTIVE COMPARATOR

Combined theta burst stimulation (TBS) of the left (intermittent TBS, iTBS) and right (continuous TBS, cTBS) dorsolateral prefrontal cortex (dlPFC; F3 and F4 according to EEG10/20 system). Each stimulation session will comprise 2 trains of 600 stimuli each applied in bursts of three pulses at 50 Hz given every 200 ms. iTBS will be applied 20 times for 2 s every 10 s. In the same session, stimulation with cTBS will be applied continuously for 40 s. Intensity of iTBS/cTBS will be standardized at 80 % of the resting motor threshold (rMT). Additionally, patients receive an electrical co-stimulation of the forehead. One electrode is fixed to FZ and the 2nd one is either fixed to the left forehead (iTBS) or the right forehead (cTBS), rectangular aligned to the upper edge of the FZ-electrode with a distance of 0.5 cm. Intensity of the co-stimulation is applied with 50% of TBS-intensity.

Device: Transcranial Magnetic Stimulation

sham stimulation

SHAM COMPARATOR

Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered

Device: Sham Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic StimulationDEVICE

MagVenture Coil Cool B70 A/P

combined iTBS/cTBS
Sham Transcranial Magnetic StimulationDEVICE

MagVenture Coil Cool B70 A/P without TMS being actively delivered

sham stimulation

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • moderate or severe unipolar depression diagnosed according to criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)
  • duration of the current episode must be ≥ 6 weeks and ≤ 2 years
  • HDRS17 ≥ 18
  • mild to moderate treatment resistance according to the Antidepressant Treatment History Form \[ATHF-SF\]. Treatment resistance is defined as having failed at least one but no more than three adequate antidepressant treatments in this episode
  • stable antidepressive medication 4 weeks before treatment or no antidepressive treatment
  • no further relevant psychiatric axis-I and/or axis-II disorder except for anxiety disorders (according to DSM-5 and SCID-5-PD)
  • no comorbid psychotic symptoms
  • ability to give consent

You may not qualify if:

  • acute suicidality (MADRS item 10 score \> 4)
  • antiepileptic drugs and/or benzodiazepines corresponding to \> 1mg lorazepam / day
  • history of brain surgery, significant and clinically relevant brain malformation or neoplasm, head injury, stroke, dementia or other neurodegenerative disorder
  • history of seizures
  • previous rTMS treatment
  • lifetime history of non-response to adequate electroconvulsive therapy (minimum of eight treatments)
  • deep brain stimulation
  • cardiac pacemakers, intracranial implant, or metal in the cranium
  • substance dependence or abuse in the past 3 months (with the exception of tobacco)
  • severe somatic comorbidity as judged by the study physician
  • pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg

Augsburg, 86156, Germany

Location

University of Leipzig, Dept. Psychiatry and Psychotherapy

Leipzig, Germany

Location

University of Munich

Munich, 80336, Germany

Location

University of Regensburg, Dept. Psychiatry and Psychotherapy

Regensburg, 93053, Germany

Location

University of Tuebingen, Dept Psychiatry and Psychotherapy

Tübingen, 72076, Germany

Location

University of Um, Dept. Psychiatry and Psychotherapy

Ulm, 89075, Germany

Location

University of Wuerzburg, Dept. Psychiatry and Psychotherapy

Würzburg, Germany

Location

Related Publications (1)

  • Plewnia C, Brendel B, Schwippel T, Nieratschker V, Ethofer T, Kammer T, Padberg F, Martus P, Fallgatter AJ. Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). Eur Arch Psychiatry Clin Neurosci. 2021 Oct;271(7):1231-1243. doi: 10.1007/s00406-021-01280-w. Epub 2021 Jun 19.

    PMID: 34146143DERIVED

Related Links

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Christian Plewnia, Prof., MD

    Department of Psychiatry and Psychotherapy, University of Tuebingen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The usage of a special active/placebo (A/P) coil in combination with an electrical co-stimulation will guarantee masking. A hard cover surrounds the A/P coil and for this reason it is not possible to see which side is the active side of the coil. By entering a randomized code into the stimulator, the operator receive information whether the coil is in the correct position or has to be flipped around. The code does not allow third parties to identify to which study arm a patient has been assigned. The concealment of the assignment remains until the statistical analysis is finished.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2020

First Posted

May 19, 2020

Study Start

September 29, 2020

Primary Completion

May 28, 2025

Study Completion

July 31, 2025

Last Updated

September 17, 2025

Record last verified: 2024-10

Locations

DE(7)