search
Back to results

Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation (TBS-D)

Primary Purpose

Major Depressive Disorder

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring major depression, theta burst stimulation, dorsolateral prefrontal cortex, randomized, sham-controlled, multicenter

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Leipzig, Dept. Psychiatry and PsychotherapyRecruiting
  • University of MunichRecruiting
  • University of Regensburg, Dept. Psychiatry and PsychotherapyRecruiting
  • University of Tuebingen, Dept Psychiatry and PsychotherapyRecruiting
  • University of Um, Dept. Psychiatry and PsychotherapyRecruiting
  • University of Wuerzburg, Dept. Psychiatry and PsychotherapyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

combined iTBS/cTBS

sham stimulation

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Remission rate after treatment
Montgomery-Asberg Depression Rating Scale (MADRS) </= 10 after treatment (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-53;higher score indicates higher level of severity)
Reduction of raw score: Clinical Global Impression (CGI)
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-7; higher score indicates higher level of severity)
Reduction of raw score: Beck Depression Inventory (BDI-II)
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-63; higher score indicates higher level of severity)
Reduction of raw score: WHO-5 well-being index
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-25; lower score indicates higher level of severity)
Work Productivity and Activity Impairment Questionnaire (WPAI)
Functionality will be assessed by Work Productivity and Activity Impairment Questionnaire (WPAI; self-rating questionnaire) at baseline, after treatment period as well as during follow-up; contains 6 questions about the effect of health problems on the ability to work and perform regular activities. Health problems are defined as any physical or emotional problem or symptom. Patients are asked to fill in the blanks or circle a number; there is no overall score;
Frequency of adverse events
Comparison of both arms in respect to number of adverse events during treatment period
Deterioration rate after treatment period
Deterioration is defined as an increase of MADRS (Montgomery-Asberg Depression Rating Scale) score of 25% compared to baseline score (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS
It will be examined whether the CTQ can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS
It will be examined whether cognitive performance measured by THINC-Integrated Tool (Thinc-it -tool; includes 4 different test covering different aspects of cognition) at baseline can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)

Full Information

First Posted
May 8, 2020
Last Updated
June 8, 2022
Sponsor
University Hospital Tuebingen
Collaborators
Federal Ministry of Health, Germany, Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany, Center of Clinical Trials, University Tuebingen, Germany, University of Ulm, Department of Psychiatry and Psychotherapy, University Regensburg, Germany, Department of Psychiatry and Psychotherapy, University Wuerzburg, Germany, Department of Psychiatry and Psychotherapy, University Munich (LMU), Germany, Department of Psychiatry and Psychotherapy, University Leipzig, Germany
search

1. Study Identification

Unique Protocol Identification Number
NCT04392947
Brief Title
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
Acronym
TBS-D
Official Title
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 29, 2020 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen
Collaborators
Federal Ministry of Health, Germany, Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany, Center of Clinical Trials, University Tuebingen, Germany, University of Ulm, Department of Psychiatry and Psychotherapy, University Regensburg, Germany, Department of Psychiatry and Psychotherapy, University Wuerzburg, Germany, Department of Psychiatry and Psychotherapy, University Munich (LMU), Germany, Department of Psychiatry and Psychotherapy, University Leipzig, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
major depression, theta burst stimulation, dorsolateral prefrontal cortex, randomized, sham-controlled, multicenter

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
236 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
combined iTBS/cTBS
Arm Type
Active Comparator
Arm Description
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.
Arm Title
sham stimulation
Arm Type
Sham Comparator
Arm Description
Setup is identical to combined active iTBS/cTBS but TBS is not actively delivered
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Intervention Description
MagVenture Coil Cool B70 A/P
Intervention Type
Device
Intervention Name(s)
Sham Transcranial Magnetic Stimulation
Intervention Description
MagVenture Coil Cool B70 A/P without TMS being actively delivered
Primary Outcome Measure Information:
Title
Response rate of Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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)
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Remission rate after treatment
Description
Montgomery-Asberg Depression Rating Scale (MADRS) </= 10 after treatment (rater questionnaire; MADRS raw score ranges between 0 and 60; the higher the score, the more severe depression)
Time Frame
6 weeks
Title
Reduction of raw score: Montgomery-Asberg Depression Rating Scale (MADRS)
Description
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Time Frame
6 weeks
Title
Reduction of raw score: Hamilton Depression Rating Scale 17 items (HDRS17)
Description
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-53;higher score indicates higher level of severity)
Time Frame
6 weeks
Title
Reduction of raw score: Clinical Global Impression (CGI)
Description
The reduction of the raw score after treatment will be compared between active TBS and sham TBS (rater questionnaire; score ranges from 0-7; higher score indicates higher level of severity)
Time Frame
6 weeks
Title
Reduction of raw score: Beck Depression Inventory (BDI-II)
Description
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-63; higher score indicates higher level of severity)
Time Frame
10 and 18 weeks
Title
Reduction of raw score: WHO-5 well-being index
Description
The reduction of the raw score during follow-up will be compared between active TBS and sham TBS (self-rating questionnaire; score ranges from 0-25; lower score indicates higher level of severity)
Time Frame
10 and 18 weeks
Title
Work Productivity and Activity Impairment Questionnaire (WPAI)
Description
Functionality will be assessed by Work Productivity and Activity Impairment Questionnaire (WPAI; self-rating questionnaire) at baseline, after treatment period as well as during follow-up; contains 6 questions about the effect of health problems on the ability to work and perform regular activities. Health problems are defined as any physical or emotional problem or symptom. Patients are asked to fill in the blanks or circle a number; there is no overall score;
Time Frame
6 and 18 weeks
Title
Frequency of adverse events
Description
Comparison of both arms in respect to number of adverse events during treatment period
Time Frame
6 weeks
Title
Deterioration rate after treatment period
Description
Deterioration is defined as an increase of MADRS (Montgomery-Asberg Depression Rating Scale) score of 25% compared to baseline score (rater questionnaire; range between 0 and 60; higher score indicates higher level of severity)
Time Frame
6 weeks
Title
Examination of the influence of Childhood Trauma Questionnaire (CTQ) at baseline as possible predictor for change of MADRS
Description
It will be examined whether the CTQ can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Time Frame
6 weeks
Title
Examination of the influence of cognitive performance at baseline as possible predictor for change of MADRS
Description
It will be examined whether cognitive performance measured by THINC-Integrated Tool (Thinc-it -tool; includes 4 different test covering different aspects of cognition) at baseline can be used for predicting treatment effect, measured by Montgomery-Asberg Depression Rating Scale (MADRS, see above)
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christian Plewnia, Prof., MD
Phone
+49707129
Ext
82311
Email
christian.plewnia@uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Plewnia, Prof., MD
Organizational Affiliation
Department of Psychiatry and Psychotherapy, University of Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Leipzig, Dept. Psychiatry and Psychotherapy
City
Leipzig
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Munich
City
Munich
ZIP/Postal Code
80336
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Regensburg, Dept. Psychiatry and Psychotherapy
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Tuebingen, Dept Psychiatry and Psychotherapy
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Um, Dept. Psychiatry and Psychotherapy
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Wuerzburg, Dept. Psychiatry and Psychotherapy
City
Wuerzburg
Country
Germany
Individual Site Status
Recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
34146143
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.
Results Reference
derived

Learn more about this trial

Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

We'll reach out to this number within 24 hrs