Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

Major Depressive Disorder Clinical Trial

— TBS-D  

Official title:

Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04392947
• Other study ID #: 01KG2003
• Status: Recruiting
• Phase: N/A
• Start date: September 29, 2020
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: University Hospital Tuebingen
• Contact: Christian Plewnia, Prof., MD
• Phone: +49707129
• Email: christian.plewnia[@]uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 236
• Est. completion date: September 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• Transcranial Magnetic Stimulation
MagVenture Coil Cool B70 A/P
• Sham Transcranial Magnetic Stimulation
MagVenture Coil Cool B70 A/P without TMS being actively delivered

Locations

Country	Name	City	State
Germany	University of Leipzig, Dept. Psychiatry and Psychotherapy	Leipzig
Germany	University of Munich	Munich
Germany	University of Regensburg, Dept. Psychiatry and Psychotherapy	Regensburg
Germany	University of Tuebingen, Dept Psychiatry and Psychotherapy	Tuebingen
Germany	University of Um, Dept. Psychiatry and Psychotherapy	Ulm
Germany	University of Wuerzburg, Dept. Psychiatry and Psychotherapy	Wuerzburg

Sponsors (9)

Lead Sponsor

Collaborator

University Hospital Tuebingen

Center of Clinical Trials, University Tuebingen, Germany, Department of Psychiatry and Psychotherapy, University Leipzig, Germany, Department of Psychiatry and Psychotherapy, University Munich (LMU), Germany, Department of Psychiatry and Psychotherapy, University Regensburg, Germany, Department of Psychiatry and Psychotherapy, University Wuerzburg, Germany, Federal Ministry of Health, Germany, Institute of Clinical Epidemiology and applied Biometry, University Tuebingen, Germany, University of Ulm

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Remission rate after treatment	Montgomery-Asberg Depression Rating Scale (MADRS)	6 weeks
Secondary	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)	6 weeks
Secondary	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)	6 weeks
Secondary	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)	6 weeks
Secondary	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)	10 and 18 weeks
Secondary	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)	10 and 18 weeks
Secondary	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;	6 and 18 weeks
Secondary	Frequency of adverse events	Comparison of both arms in respect to number of adverse events during treatment period	6 weeks
Secondary	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)	6 weeks
Secondary	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)	6 weeks
Secondary	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)	6 weeks