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Stimulation of Parieto-hippocampal Connectivity in Patients With Major Depressive Disorder

Not Applicable
Completed
Conditions
Depression
Depressive Disorder, Major
Depressive Disorder
Depressive Episode
Interventions
Device: active rTMS over DLPFC
Device: Add-on active rTMS over LPC
Device: Add-on sham rTMS
Device: Add-on active rTMS over DLPFC
Registration Number
NCT04081519
Lead Sponsor
University Hospital, Bonn
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
53
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DLPFC-DLPFCactive rTMS over DLPFC15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over DLPFC
DLPFC-LPCAdd-on active rTMS over LPC15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over LPC
DLPFC-SHAMactive rTMS over DLPFC15 sessions of active rTMS over DLPFC + 15 sessions of sham rTMS over DLPFC or LPC
DLPFC-SHAMAdd-on sham rTMS15 sessions of active rTMS over DLPFC + 15 sessions of sham rTMS over DLPFC or LPC
DLPFC-LPCactive rTMS over DLPFC15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over LPC
DLPFC-DLPFCAdd-on active rTMS over DLPFC15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over DLPFC
Primary Outcome Measures
NameTimeMethod
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 fMRI3 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 paradigm3 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 Outcome Measures
NameTimeMethod
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 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.

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 task-based fMRI activation during social touch paradigm3 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 task-based fMRI activation during emotional processing paradigm3 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.

Trial Locations

Locations (1)

Klinik und Poliklinik für Psychiatrie und Psychotherapie

🇩🇪

Bonn, Germany

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