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Resting-state Functional Connectivity Throughout a Course of iTBS in Major Depression

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ClinicalTrials.gov Identifier: NCT03944213
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : May 25, 2022
Sponsor:
Collaborators:
Clemens Mielacher, University Hospital, Bonn
Maximilian Kiebs, University Hospital, Bonn
Information provided by (Responsible Party):
Rene Hurlemann, University Hospital, Bonn

Study Description
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Brief Summary:
This study aims to investigate changes in functional connectivity over a four week treatment course with intermittent theta burst stimulation (iTBS) in patients with major depressive disorder (MDD). To this end, seven weekly resting-state fMRI (rs-fMRI) scans at 7 tesla (7T) will precede, accompany and follow the iTBS treatment course. By obtaining several samples of the modulatory effects of iTBS on functional connectivity networks and simultaneous measurements of the depressive symptoms it will be possible to assess the time course of changes in connectivity across different networks, and to assess the overall relationship between the network modulation and the antidepressant effects of the treatment over time.

Condition or disease Intervention/treatment
Depression Depressive Disorder Depressive Disorder, Major Depressive Episode Device: intermittent theta burst stimulation (iTBS)

Detailed Description:

The immense disease burden of major depressive disorder (MDD) and unsatisfactory response rates to pharmacological and psychological interventions highlight the need for further development of treatment alternatives. The development of these alternatives relies on an understanding of the pathophysiology of depression, which has, despite considerable efforts, remained largely elusive. Findings have converged on the proposition that depression cannot be attributed to a singular factor and is better understood as a dysfunctional interaction of multiple parameters. At the neural level, depression is described as a dysfunction of several cortical and sub-cortical networks associated with affective salience, cognitive control and self-reverential thoughts. Encouragingly, several studies have shown that pathological alterations in one of these networks, the Default Mode network, may normalize following several weeks of treatment using repetitive transcranial magnetic stimulation (rTMS), an accepted treatment for major depression.

The present study aims to elucidate the time course of this modulatory effect on the different networks showing pathological connectivity profiles. Specifically, our aim is to obtain several measurements of functional connectivity and concomitant measures of the symptoms of depression prior to, throughout, and following the 4 week treatment course of iTBS, a faster but equally effective non-invasive brain stimulation technique compared to rTMS. Due to the fact that weekly changes in network connectivity are expected to be relatively small, the stronger BOLD Signal at 7T and the fact that peak temporal correlation coefficients calculated between network nodes have been shown to be significantly higher at 7T than 3T (e.g.) in the Default Mode network should greatly aid in detecting these differences. At each of the 7 measurement time points, fluctuations of BOLD signal will be recorded during a rs-fMRI scan lasting about 15 minutes. Our approach will allow to characterize the temporal profiles of the antidepressant effects of iTBS, thereby furthering our understanding of the mechanism by which iTBS contributes to the normalization of pathological neural connectivity and the reduction of depression symptoms. This proposed longitudinal functional imaging of therapeutic changes is highly relevant to the field of clinical neuroscience and should further advance our understanding of the pathophysiology of depression.

Study Design
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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Resting-state Functional Connectivity Throughout a Course of iTBS in Major Depression
Actual Study Start Date : July 23, 2018
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : June 1, 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
MDD patients Device: intermittent theta burst stimulation (iTBS)
20 sessions of iTBS
Healthy controls


Outcome Measures
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Primary Outcome Measures :
  1. Change in functional connectivity coefficients based on rs-fMRI over 7 timepoints. [ Time Frame: Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement. ]
    Seed-to-voxel functional connectivity analysis of rs-fMRI data.


Secondary Outcome Measures :
  1. Change in depression severity as measured by the Hamilton Depression Rating Scale (HDRS-17) over 7 timepoints. [ Time Frame: Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement. ]
    Remission defined as HDRS-17 score (range: 0 to 52) of less than or equal to 8 after the iTBS course. Response defined as a reduction of at least 50% from baseline in HDRS-17 score after treatment.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Outpatients at the psychiatric hospital of the University Hospital Bonn. The patients diagnosis of major depressive disorder will be verified via the structured clinical interview for DSM-5. iTBS protocols in line with international standards administered by a trained professional.

Additionally, a healthy control sample is included in the study.

Criteria

Inclusion Criteria:

  • Participant is able to provide consent.
  • Diagnosis of Major Depressive Disorder according to DSM-V criteria.
  • The duration of the current episode is at least four weeks and no more than five years.
  • During the current episode, at least one antidepressant (adequate duration and dosage) was not effective OR at least two antidepressants were intolerable due to side effects.

Exclusion Criteria:

  • The participant does not fulfill requirements for iTBS treatment according to safety guidelines.
  • Cardiac or neurological surgery, active implants, metal parts within the body, claustrophobia.
  • Pregnancy or breast-feeding.
  • Psychiatric illness, e.g. substance abuse, psychosis, bipolar disorder, anorexia, obsessive compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, personality disorder.
  • Antipsychotic medication not approved for the treatment of depression.
  • Acute suicidality.
  • Conditions related to increased intracranial pressure.
  • Brain injury or stroke.
  • History of epilepsy in patient or in first-degree relative.
  • Cerebral aneurysm.
  • Neurological illness (e.g. dementia (score of less than 25 in Mini Mental State Exam), Parkinson's disease, chorea huntington, multiple sclerosis).
  • Course of electroconvulsive therapy (ECT) within the last three months
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944213


Contacts
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Contact: Clemens Mielacher, Mag. +49 228 287 11519 clemens.mielacher@ukbonn.de
Contact: Maximilian Kiebs, M.Sc. +49 228 287 19710 m.kiebs@ukbonn.de

Locations
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Germany
Klinik und Poliklinik für Psychiatrie und Psychotherapie Recruiting
Bonn, Germany
Contact: Clemens Mielacher, Mag.    +49 228 287 11519    clemens.mielacher@ukbonn.de   
Contact: Maximilian Kiebs, M.Sc.    +49 228 287 19710    m.kiebs@ukbonn.de   
Sponsors and Collaborators
University Hospital, Bonn
Clemens Mielacher, University Hospital, Bonn
Maximilian Kiebs, University Hospital, Bonn
Investigators
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Principal Investigator: René Hurlemann, Prof. University Hospital, Bonn
More Information
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Publications:

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Responsible Party: Rene Hurlemann, Chair of the Medical Psychology Division and Deputy Chair of the Department of Psychiatry, University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT03944213    
Other Study ID Numbers: DepRest
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rene Hurlemann, University Hospital, Bonn:
Transcranial Magnetic Stimulation
Theta Burst Stimulation
rTMS
TBS
resting-state fMRI
Additional relevant MeSH terms:
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Disease
Depression
Depressive Disorder
Depressive Disorder, Major
 Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders