An interventional study of theta-burst stimulation using a MagPro X1000 and sham stimulation using a MagPro X1000 in Treatment Resistant Depression, sponsored by Rupert Lanzenberger. Status unknown at 1 site in Austria. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-08-16.
Sponsored by Rupert Lanzenberger · Not applicable, Interventional, and Treatment
Background:
Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS) holds promise as an effective treatment for treatment resistant depression (TRD). rTMS has been linked to neuroplastic changes as shown using magnetic resonance imaging (MRI) and positron emission tomography (PET). Alterations in serotonin-1A receptor expression (5-HT1A) have been linked to major depression. Moreover, changes in 5-HT1A receptor binding - observed after pharmacological treatment, as well as after electroconvulsive therapy - has been linked to neuronal adaptations in response to these antidepressant treatments.
Objectives of the study:
Here, the aim is to investigate the effects of TBS over left and right dorsolateral prefrontal cortex on the 5-HT1A receptor binding in patients with TRD using PET. In addition, effects of iTBS on brain structure and function will be determined using functional, structural and perfusion MRI.
Study population:
80 patients with TRD who maintain their original medication regimen will be recruited.
Study design:
Longitudinal, randomized and double-blind clinical trial. 40 patients will receive active TBS, 40 patients will receive sham TBS for treatment duration of three weeks. Before and after three weeks of treatment, patients will be scanned using MRI and PET with the highly specific and selective radiotracer [carbonyl-11C]WAY100635. A follow-up visit and final examination will be performed 2 and 4 weeks after treatment for the active TBS group, respectively. Patients in the sham TBS arm will receive active TBS treatment immediately after the second MRI and PET scan.
Relevance and implications of the study:
This will be the worldwide first multimodal imaging study to investigate the effects of TBS on serotonin-1A receptor binding in TRD using PET. Thus, the study will add crucial knowledge to the existing literature on the effects of TMS on brain structure and function, related to antidepressant efficacy. Moreover, by combining molecular imaging of serotonergic neurotransmission with structural and functional MRI, the proposed study will increase the investigators knowledge on the serotonergic role in shaping brain morphology, microstructure and structural/functional connectivity. Taken together, the study has the potential to contribute to the development of personalized treatment, the reduction of personal suffering and the reduction of costs and occupational disability.
Exclusion Criteria:
40 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements
Device: theta-burst stimulation using a MagPro X1000
40 patients with TRD will receive sham stimulation using a MagPro X1000 between the two PET measurements. After the second PET scan they will receive active TBS
Device: sham stimulation using a MagPro X1000
TBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS over left DLPFC: 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. Trains will be repeated 20 to reach a total number of 600 pulses per session. cTBS over right DLPFC: cTBS will comprise uninterrupted bursts to reach a total number of 600 pulses per session. Two sessions per day, separated by 60 minutes; 30 Sessions in total over 3 weeks.
Also known as: repetitive transcranial magnetic stimulation
Sham TBS with the coil set at 45° against the skull will be performed over left and right dorsolateral prefrontal cortex for a period of three weeks
Also known as: sham transcranial magnetic stimulation
Regional 5-HT1A receptor binding
5-HT1A receptor binding using the radioligand \[carbonyl-11C\]WAY100635
Time frame: before and after 3 weeks of TBS treatment
Regional white matter microstructure using DWI-TBSS
The analysis will be performed using tract-based spatial statistics
Time frame: before and after 3 weeks of TBS treatment
Regional white matter microstructure using DWI-Tractography
Tractography will be performed
Time frame: before and after 3 weeks of TBS treatment
Regional grey matter volume using MRI
The analysis will be done using voxel-based morphometry
Time frame: before and after 3 weeks of TBS treatment
Regional brain perfusion
Regional brain perfusion will be evaluated using Arterial Spin Labeling, ASL
Time frame: before and after 3 weeks of TBS treatment
Functional connectivity at rest and during tasks
Functional connectivity will be evaluated using resting state and task fMRI
Time frame: before and after 3 weeks of TBS treatment
Depression score using the Hamilton Depression Rating Scale
Depression will be evaluated using the Hamilton Depression Rating Scale
Time frame: before and after 3 weeks of TBS treatment
Depression score using the Beck Depression Inventory
Depression will be evaluated using the Beck Depression Inventory
Time frame: before and after 3 weeks of TBS treatment
Global physical activity
assessed using the WHO global physical assessment GPAQ
Time frame: before and after 3 weeks of TBS treatment
Plan to share: Yes — A database that also includes data from this study will be created
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Rupert Lanzenberger