TBS in Major Depression

Theta-burst Transcranial Magnetic Stimulation for the Treatment of Major Depression

Background Major depression is associated with morbidity and increased mortality. Along with the psychological strain depression represents a high socioeconomic burden costing Europe more than €113 billion/year. About one third of patients do not respond to appropriate therapy. Theta-burst stimulation (TBS), a form of transcranial magnetic stimulation is an emerging treatment for patients for whom pharmacological treatment is ineffective or not appropriate. Based on two different theories of prefrontal dysfunction two TBS-protocols should have the most antidepressant effects. However, no study so far has compared the two approaches or systematically investigated their differential effects on brain function and on a symptom level.

Objectives of the study The aim of this study is to test two TBS protocols on symptom improvement and associated brain function in patients with treatment resistant depression (TRD): iTBS over bilateral DLPFC and iTBS over left and cTBS over right DLPFC. As stimulation over non-motor regions offers no direct readout, fMRI at baseline and after treatment will be harnessed to quantify an effect on brain activity and functional network metrics.

Study population 80 patients with TRD will be enrolled with 40 patients receiving the one, and 40 patients receiving the other TBS protocol for a treatment period of three weeks.

Study design The study is designed as a longitudinal, randomized and double-blind clinical trial. At baseline and after treatment, patients will undergo psychiatric testing using several symptom scales including the Hamilton Depression Rating Scale (HAMD-17), the Beck Depression Inventory (BDI-II), the Inventory of Depressive Symptomatology (IDS-C) and the State-Trait Anxiety Inventory (STAI). Changes in HAMD-17 scores are defined as primary endpoint. Moreover MRI scans before and after treatment will include structural and functional MRI sequences as well as diffusion weighted imaging (DWI) sequence. Functional connectivity and BOLD responses will serve as primary imaging endpoints. A follow-up visit 2 weeks and a final examination 4 weeks after treatment will elucidate durability of effects.

Relevance and implications of the study By investigating which approach is superior for which symptoms our study will contribute to the development of personalized treatment, the reduction of personal suffering and the reduction of costs and occupational disability.

Study Overview

• Status: Unknown
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Device: theta-burst stimulation (TBS) using a MagPro X1000; Device: theta-burst stimulation (TBS) using a MagPro X1000

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Psychiatry and Psychotherapy, Medical University of Vienna
    • Contact: Rupert Lanzenberger, A/Prof.; Phone Number: 3825 +43 40400; Email: rupert.lanzenberger@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM-5 diagnosis of a single or recurrent major depression
• Failure of at least two adequate antidepressant treatments
• HAMD-17 total score of ≥ 23 and a Clinical Global Impression Scale (CGI-S) of ≥ 4
• Stable psychopharmacological treatment within 2 weeks prior inclusion
• Age 18-65 years
• Right-handedness (assessed with the Edinburgh Handedness Inventory)

Exclusion Criteria:

• Seizures in medical history
• Medical history of major systemic illness, neurological disorders and previous brain injuries
• Ferromagnetic implants, cardiac pacemaker, deep brain stimulation and other common MRI and TMS exclusion criteria
• Current psychotic symptoms
• Substance abuse or dependence within last 3 months
• Borderline personality disorder (based on DSM-5 criteria)
• Pregnancy
• Active suicidal intent
• Benzodiazepines other than Lorazepam < 2mg/d
• failure to comply with the study protocol or to follow the instructions of the investigating team

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: left iTBS and right cTBS; 40 patients will receive intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS (cTBS) over the right DLPFC	Device: theta-burst stimulation (TBS) using a MagPro X1000; iTBS over left and cTBS over right dorsolateral prefrontal cortex for a period of three weeks. iTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. cTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in a single 40s train; one session will comprise left iTBS and right cTBS. There will be two sessions daily with 60 min in between sessions; Other Names: transcranial magnetic stimulation; Device: theta-burst stimulation (TBS) using a MagPro X1000; iTBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS consists of 3-pulse 50 Hz bursts which will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. One session will comprise left and right iTBS. There will be two sessions daily with 60 min in between sessions; Other Names: transcranial magnetic stimulation
Active Comparator: left and right iTBS; 40 patients will receive intermittent theta-burst stimulation (iTBS) over the left and right dorsolateral prefrontal cortex (DLPFC)	Device: theta-burst stimulation (TBS) using a MagPro X1000; iTBS over left and cTBS over right dorsolateral prefrontal cortex for a period of three weeks. iTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. cTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in a single 40s train; one session will comprise left iTBS and right cTBS. There will be two sessions daily with 60 min in between sessions; Other Names: transcranial magnetic stimulation; Device: theta-burst stimulation (TBS) using a MagPro X1000; iTBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS consists of 3-pulse 50 Hz bursts which will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. One session will comprise left and right iTBS. There will be two sessions daily with 60 min in between sessions; Other Names: transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HAMD	Hamilton depression rating scale	<1 month
BDI-II	Beck Depression Inventory	<1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional white matter microstructure using DWI	White matter microstructure will be investigated using diffusion tensor imaging and analyzed using tract-based spatial statistics and tractography	<1 month
Regional grey matter volume and using MRI	Regional grey matter volume will be investigated using voxel-based morphometry	<1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global physical activity	assessed using Clinical Global Impression Scale (CGI-S)	<1 month

Collaborators and Investigators

• Sponsor: Rupert Lanzenberger

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: PSY-NIL-0008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No