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

May 24, 2022 updated by: Rene Hurlemann, University Hospital, Bonn
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Maximilian Kiebs, M.Sc.
  • Phone Number: +49 228 287 19710
  • Email: m.kiebs@ukbonn.de

Study Locations

  • Germany
      • Bonn, Germany
        • Recruiting
        • Klinik und Poliklinik für Psychiatrie und Psychotherapie
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Six weekly measurements starting 1 week before first iTBS treatment session, one follow-up measurement four weeks after last measurement.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bonn

Collaborators

Clemens Mielacher, University Hospital, Bonn
Maximilian Kiebs, University Hospital, Bonn

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 23, 2018

Primary Completion (ANTICIPATED)

February 1, 2023

Study Completion (ANTICIPATED)

June 1, 2024

Study Registration Dates

First Submitted

May 7, 2019

First Submitted That Met QC Criteria

May 8, 2019

First Posted (ACTUAL)

May 9, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 25, 2022

Last Update Submitted That Met QC Criteria

May 24, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DepRest

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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