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

Sponsor
University Hospital, Bonn (Other)
Overall Status
Completed
CT.gov ID
NCT04081519
Collaborator
Clemens Mielacher, University Hospital, Bonn (Other)
53
1
3
22.6
2.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Device: active rTMS over DLPFC
  • Device: Add-on active rTMS over DLPFC
  • Device: Add-on active rTMS over LPC
  • Device: Add-on sham rTMS
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Stimulation of Parieto-hippocampal Connectivity in Patients With Major Depressive Disorder
Actual Study Start Date :
Aug 2, 2016
Actual Primary Completion Date :
Mar 31, 2018
Actual Study Completion Date :
Jun 22, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: DLPFC-DLPFC

15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over DLPFC

Device: active rTMS over DLPFC
15 sessions of active rTMS over DLPFC

Device: Add-on active rTMS over DLPFC
15 additional sessions of active rTMS over DLPFC

Experimental: DLPFC-LPC

15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over LPC

Device: active rTMS over DLPFC
15 sessions of active rTMS over DLPFC

Device: Add-on active rTMS over LPC
15 additional sessions of active rTMS over LPC

Sham Comparator: DLPFC-SHAM

15 sessions of active rTMS over DLPFC + 15 sessions of sham rTMS over DLPFC or LPC

Device: active rTMS over DLPFC
15 sessions of active rTMS over DLPFC

Device: Add-on sham rTMS
15 additional sessions of sham rTMS over DLPFC or LPC

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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 Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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'.

  5. 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.

  6. 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.

  7. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Klinik und Poliklinik für Psychiatrie und Psychotherapie Bonn Germany

Sponsors and Collaborators

  • University Hospital, Bonn
  • Clemens Mielacher, University Hospital, Bonn

Investigators

  • Principal Investigator: René Hurlemann, Prof., University Hospital, Bonn

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Rene Hurlemann, Chair of the Medical Psychology Division and Deputy Chair of the Department of Psychiatry, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT04081519
Other Study ID Numbers:
  • SHIP
First Posted:
Sep 9, 2019
Last Update Posted:
Aug 4, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Rene Hurlemann, Chair of the Medical Psychology Division and Deputy Chair of the Department of Psychiatry, University Hospital, Bonn
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 4, 2021