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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04081519
• Other study ID #: SHIP
• Status: Completed
• Phase: N/A
• Start date: August 2, 2016
• Est. completion date: June 22, 2018

Study information

• Verified date: July 2021
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 22, 2018
• Est. primary completion date: March 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Episode
• Disease

Intervention

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

Locations

Country	Name	City	State
Germany	Klinik und Poliklinik für Psychiatrie und Psychotherapie	Bonn

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bonn	Clemens Mielacher, University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View 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. Epub 2005 Sep 14. — View 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. — View Citation

Lefaucheur JP, André-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, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	3 days prior to first rTMS session and 3 days after last rTMS session, follow-up after 4, 8 and 12 weeks
Secondary	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.	3 days prior to first rTMS session and 3 days after last rTMS session
Secondary	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.	3 days prior to first rTMS session and 3 days after last rTMS session
Secondary	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'.	3 days prior to first rTMS session and 3 days after last rTMS session
Secondary	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.	3 days prior to first rTMS session and 3 days after last rTMS session
Secondary	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.	3 days prior to first rTMS session and 3 days after last rTMS session
Secondary	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.	3 days prior to first rTMS session and 3 days after last rTMS session