Clinical trial NCT04392947: Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
Official title: Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Keywords: major depression
theta burst stimulation
dorsolateral prefrontal cortex
randomized
sham-controlled
multicenter
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: Federal Ministry of Health, Germany
name: Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany
name: Center of Clinical Trials, University Tuebingen, Germany
name: University of Ulm
name: Department of Psychiatry and Psychotherapy, University Regensburg, Germany
name: Department of Psychiatry and Psychotherapy, University Wuerzburg, Germany
name: Department of Psychiatry and Psychotherapy, University Munich (LMU), Germany
name: Department of Psychiatry and Psychotherapy, University Leipzig, Germany
name: Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg, Germany
First posted: 2020-05-19
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 6 weeks
Secondary outcomes:
measure: Remission rate after treatment
timeFrame: 6 weeks
measure: Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 6 weeks
measure: Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)
timeFrame: 6 weeks
measure: Reduction of raw score: Clinical Global Impression (CGI)
timeFrame: 6 weeks
measure: Reduction of raw score: Beck Depression Inventory (BDI-II)
timeFrame: 10 and 18 weeks
measure: Reduction of raw score: WHO-5 well-being index
timeFrame: 10 and 18 weeks
measure: Work Productivity and Activity Impairment Questionnaire (WPAI)
timeFrame: 6 and 18 weeks
measure: Frequency of adverse events
timeFrame: 6 weeks
measure: Deterioration rate after treatment period
timeFrame: 6 weeks
measure: Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS
timeFrame: 6 weeks
measure: Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg
city: Leipzig
country: Germany
facility: University of Leipzig, Dept. Psychiatry and Psychotherapy
city: Munich
country: Germany
facility: University of Munich
city: Regensburg
country: Germany
facility: University of Regensburg, Dept. Psychiatry and Psychotherapy
city: Tuebingen
country: Germany
facility: University of Tuebingen, Dept Psychiatry and Psychotherapy
city: Ulm
country: Germany
facility: University of Um, Dept. Psychiatry and Psychotherapy
city: Wuerzburg
country: Germany
facility: University of Wuerzburg, Dept. Psychiatry and Psychotherapy
Study officials:
affiliation: Department of Psychiatry and Psychotherapy, University of Tuebingen
name: Christian Plewnia, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.