Depression, Depressive Disorder, Depressive Disorder, Major, Depressive Episode
Conditions
Keywords
Repetitive Transcranial Magnetic Stimulation, Theta Burst Stimulation, rTMS, TBS, resting-state fMRI, functional connectivity
Brief summary
This study aims to investigate the effects of individualized repetitive transcranial magnetic stimulation (rTMS) of parieto-hippocampal functional connectivity in patients with major depressive disorder (MDD). Specifically, patients will be randomized to one of three groups and will receive 15 days of rTMS over three weeks. Each day they will receive one active session of rTMS over the dorsolateral parietal cortex (DLPFC) and depending on group assignment another session either A) active rTMS over DLPFC, B) active rTMS over left and right lateral parietal cortex (LPC), or C) sham rTMS over DLPFC or LPC. Stimulation targets in the LPC will be individualized for each patient based on their resting-state functional connectivity between the hippocampus and LPC. Clinical, neuropsychological and fMRI data will be acquired before and after the treatment course.
Interventions
DEVICEactive rTMS over DLPFC
15 sessions of active rTMS over DLPFC
DEVICEAdd-on active rTMS over DLPFC
15 additional sessions of active rTMS over DLPFC
DEVICEAdd-on active rTMS over LPC
15 additional sessions of active rTMS over LPC
DEVICEAdd-on sham rTMS
15 additional sessions of sham rTMS over DLPFC or LPC
Sponsors
Clemens Mielacher, University Hospital, Bonn
University Hospital, Bonn
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* fulfilled criteria for unipolar major depressive disorder for at least four weeks * did not respond to a minimum of one or did not tolerate a minimum of two antidepressants in the current episode
Exclusion criteria
* metal in the brain or the skull * cardiac pacemaker or intracardiac lines * medication infusion devices * heart or brain surgery * pregnancy * substance induced depression * history of substance abuse * psychotic episodes * bipolar disorder * anorexia * posttraumatic stress disorder (current or within the last 12 months) * claustrophobia * any condition resulting in increased intracranial pressure * traumatic brain injury * history of epilepsy * cerebral aneurysms * dementia * Morbus Parkinson * Chorea Huntington * multiple sclerosis * stroke or transient ischemic attack (within the last 2 years) * previous antidepressive treatment with rTMS, electroconvulsive therapy (within the last 3 months), vagus nerve stimulation or deep brain stimulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in depression severity as measured by the Hamilton Depression Rating Scale (HAMD-17) | Four measurement time points with a seven-day interval starting on the first day of stimulation, and ending three days after the last day of stimulation | Remission defined as HAMD-17 score (range: 0 to 52, lower scores represent better outcome) of less than or equal to 8 after the rTMS course. Response defined as a reduction of at least 50% from baseline in HAMD-17 score after treatment. |
| Change in functional connectivity coefficients based on resting-state fMRI | 3 days prior to first rTMS session and 3 days after last rTMS session | Seed-to-voxel and ROI-to-ROI functional connectivity analysis of rs-fMRI data. |
| Change in task-based fMRI activation during associative memory paradigm | 3 days prior to first rTMS session and 3 days after last rTMS session | Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal encoding and retrieval with a focus on hippocampal regions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in visual sustained attention as assessed by the Rapid Visual Information Processing (RVP) | 3 days prior to first rTMS session and 3 days after last rTMS session | Subjects will be assessed in the domain of visual sustained attention by undergoing computorized neurological testing. Outcome varible is the target sensitivity A'. |
| Change in working memory as assessed by the Spatial Working Memory (SWM) | 3 days prior to first rTMS session and 3 days after last rTMS session | Subjects will be assessed in the domain of working memory by undergoing computorized neurological testing. Outcome varible is the total number of errors. |
| Change in depression severity as measured by the Beck's Depression Inventory (BDI-II) | 3 days prior to first rTMS session and 3 days after last rTMS session, follow-up after 4, 8 and 12 weeks | Remission defined as BDI-II score (range: 0 to 63, lower scores represent better outcome) of less than or equal to 12 after the rTMS course. Response defined as a reduction of at least 50% from baseline in BDI-II score after treatment. |
| Change in task-based fMRI activation during emotional processing paradigm | 3 days prior to first rTMS session and 3 days after last rTMS session | Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal while participants perform an emotional processing task. |
| Change in task-based fMRI activation during social touch paradigm | 3 days prior to first rTMS session and 3 days after last rTMS session | Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal while participants receive tactile stimulation. |
| Change in visual memory as assessed by the Delayed Matching to Sample test (DMS) | 3 days prior to first rTMS session and 3 days after last rTMS session | Subjects will be assessed in the domain of visual memory by undergoing computorized neurological testing. Outcome varible is percentage of correct answers. |
| Change in spatial planning as assessed by the One Touch Stockings of Cambridge (OTS) | 3 days prior to first rTMS session and 3 days after last rTMS session | Subjects will be assessed in the domain of spatial planning by undergoing computorized neurological testing. Outcome varible is the mean number of choices to correct answer. |
Countries
Germany
Outcome results
None listed