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

Primary Purpose

Depression, Depressive Disorder, Depressive Episode

Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
active rTMS over DLPFC
Add-on active rTMS over DLPFC
Add-on active rTMS over LPC
Add-on sham rTMS
Sponsored by
University Hospital, Bonn
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Repetitive Transcranial Magnetic Stimulation, Theta Burst Stimulation, rTMS, TBS, resting-state fMRI, functional connectivity

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Klinik und Poliklinik für Psychiatrie und Psychotherapie

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Sham Comparator

Arm Label

DLPFC-DLPFC

DLPFC-LPC

DLPFC-SHAM

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Change in depression severity as measured by the Hamilton Depression Rating Scale (HAMD-17)
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
Seed-to-voxel and ROI-to-ROI functional connectivity analysis of rs-fMRI data.
Change in task-based fMRI activation during associative memory paradigm
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

Change in depression severity as measured by the Beck's Depression Inventory (BDI-II)
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)
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)
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)
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)
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 paradigm
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 paradigm
Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal while participants perform an emotional processing task.

Full Information

First Posted
August 27, 2019
Last Updated
July 28, 2021
Sponsor
University Hospital, Bonn
Collaborators
Clemens Mielacher, University Hospital, Bonn
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1. Study Identification

Unique Protocol Identification Number
NCT04081519
Brief Title
Stimulation of Parieto-hippocampal Connectivity in Patients With Major Depressive Disorder
Official Title
Stimulation of Parieto-hippocampal Connectivity in Patients With Major Depressive Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 2, 2016 (Actual)
Primary Completion Date
March 31, 2018 (Actual)
Study Completion Date
June 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Bonn
Collaborators
Clemens Mielacher, University Hospital, Bonn

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Depressive Disorder, Depressive Episode, Depressive Disorder, Major
Keywords
Repetitive Transcranial Magnetic Stimulation, Theta Burst Stimulation, rTMS, TBS, resting-state fMRI, functional connectivity

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DLPFC-DLPFC
Arm Type
Active Comparator
Arm Description
15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over DLPFC
Arm Title
DLPFC-LPC
Arm Type
Experimental
Arm Description
15 sessions of active rTMS over DLPFC + 15 sessions of active rTMS over LPC
Arm Title
DLPFC-SHAM
Arm Type
Sham Comparator
Arm Description
15 sessions of active rTMS over DLPFC + 15 sessions of sham rTMS over DLPFC or LPC
Intervention Type
Device
Intervention Name(s)
active rTMS over DLPFC
Intervention Description
15 sessions of active rTMS over DLPFC
Intervention Type
Device
Intervention Name(s)
Add-on active rTMS over DLPFC
Intervention Description
15 additional sessions of active rTMS over DLPFC
Intervention Type
Device
Intervention Name(s)
Add-on active rTMS over LPC
Intervention Description
15 additional sessions of active rTMS over LPC
Intervention Type
Device
Intervention Name(s)
Add-on sham rTMS
Intervention Description
15 additional sessions of sham rTMS over DLPFC or LPC
Primary Outcome Measure Information:
Title
Change in depression severity as measured by the Hamilton Depression Rating Scale (HAMD-17)
Description
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.
Time Frame
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
Title
Change in functional connectivity coefficients based on resting-state fMRI
Description
Seed-to-voxel and ROI-to-ROI functional connectivity analysis of rs-fMRI data.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in task-based fMRI activation during associative memory paradigm
Description
Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal encoding and retrieval with a focus on hippocampal regions.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Secondary Outcome Measure Information:
Title
Change in depression severity as measured by the Beck's Depression Inventory (BDI-II)
Description
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.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session, follow-up after 4, 8 and 12 weeks
Title
Change in visual memory as assessed by the Delayed Matching to Sample test (DMS)
Description
Subjects will be assessed in the domain of visual memory by undergoing computorized neurological testing. Outcome varible is percentage of correct answers.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in spatial planning as assessed by the One Touch Stockings of Cambridge (OTS)
Description
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.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in visual sustained attention as assessed by the Rapid Visual Information Processing (RVP)
Description
Subjects will be assessed in the domain of visual sustained attention by undergoing computorized neurological testing. Outcome varible is the target sensitivity A'.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in working memory as assessed by the Spatial Working Memory (SWM)
Description
Subjects will be assessed in the domain of working memory by undergoing computorized neurological testing. Outcome varible is the total number of errors.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in task-based fMRI activation during social touch paradigm
Description
Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal while participants receive tactile stimulation.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session
Title
Change in task-based fMRI activation during emotional processing paradigm
Description
Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal while participants perform an emotional processing task.
Time Frame
3 days prior to first rTMS session and 3 days after last rTMS session

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René Hurlemann, Prof.
Organizational Affiliation
University Hospital, Bonn
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinik und Poliklinik für Psychiatrie und Psychotherapie
City
Bonn
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22658708
Citation
Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
Results Reference
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PubMed Identifier
25170153
Citation
Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.
Results Reference
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PubMed Identifier
29726344
Citation
Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26. Erratum In: Lancet. 2018 Jun 23;391(10139):e24.
Results Reference
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PubMed Identifier
25034472
Citation
Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.
Results Reference
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PubMed Identifier
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Citation
Daumann J, Fischermann T, Heekeren K, Henke K, Thron A, Gouzoulis-Mayfrank E. Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users. Psychopharmacology (Berl). 2005 Aug;180(4):607-11. doi: 10.1007/s00213-004-2002-8. Epub 2005 Sep 14.
Results Reference
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Stimulation of Parieto-hippocampal Connectivity in Patients With Major Depressive Disorder

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