NCT04081519

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
53

participants targeted

Target at P25-P50 for not_applicable depression

Timeline
Completed

Started Aug 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 2, 2016

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2018

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 22, 2018

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

August 27, 2019

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 9, 2019

Completed
Last Updated

August 4, 2021

Status Verified

July 1, 2021

Enrollment Period

1.7 years

First QC Date

August 27, 2019

Last Update Submit

July 28, 2021

Conditions

DepressionDepressive DisorderDepressive EpisodeDepressive Disorder, Major

Keywords

Repetitive Transcranial Magnetic StimulationTheta Burst StimulationrTMSTBSresting-state fMRIfunctional connectivity

Outcome Measures

Primary Outcomes (3)

  • 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.

    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

  • Change in functional connectivity coefficients based on resting-state fMRI

    Seed-to-voxel and ROI-to-ROI functional connectivity analysis of rs-fMRI data.

    3 days prior to first rTMS session and 3 days after last rTMS session

  • 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.

    3 days prior to first rTMS session and 3 days after last rTMS session

Secondary Outcomes (7)

  • 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

  • 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

  • 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

  • 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

  • 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

  • +2 more secondary outcomes

Study Arms (3)

DLPFC-DLPFC

ACTIVE COMPARATOR

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

Device: active rTMS over DLPFCDevice: Add-on active rTMS over DLPFC

DLPFC-LPC

EXPERIMENTAL

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

Device: active rTMS over DLPFCDevice: Add-on active rTMS over LPC

DLPFC-SHAM

SHAM COMPARATOR

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

Device: active rTMS over DLPFCDevice: Add-on sham rTMS

Interventions

active rTMS over DLPFCDEVICE

15 sessions of active rTMS over DLPFC

DLPFC-DLPFCDLPFC-LPCDLPFC-SHAM
Add-on active rTMS over DLPFCDEVICE

15 additional sessions of active rTMS over DLPFC

DLPFC-DLPFC
Add-on active rTMS over LPCDEVICE

15 additional sessions of active rTMS over LPC

DLPFC-LPC
Add-on sham rTMSDEVICE

15 additional sessions of sham rTMS over DLPFC or LPC

DLPFC-SHAM

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Klinik und Poliklinik für Psychiatrie und Psychotherapie

Bonn, Germany

Location

Related Publications (5)

  • 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.

    PMID: 22658708BACKGROUND

  • 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.

    PMID: 25170153BACKGROUND

  • 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.

    PMID: 29726344BACKGROUND

  • 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.

    PMID: 25034472BACKGROUND

  • 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.

    PMID: 15372137BACKGROUND

MeSH Terms

Conditions

DepressionDepressive DisorderDepressive Disorder, Major

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorMood DisordersMental Disorders

Study Officials

  • René Hurlemann, Prof.

    University Hospital, Bonn

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chair of the Medical Psychology Division and Deputy Chair of the Department of Psychiatry

Study Record Dates

First Submitted

August 27, 2019

First Posted

September 9, 2019

Study Start

August 2, 2016

Primary Completion

March 31, 2018

Study Completion

June 22, 2018

Last Updated

August 4, 2021

Record last verified: 2021-07

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)