Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

August 7, 2018 updated by: Rajamannar Ramasubbu, University of Calgary

Using Multiple Brain-based Biomarkers to Validate and Predict Response to Theta Burst Stimulation as a New Treatment for Major Depressive Disorder

This study investigates the brain-based biomarkers of treatment response to accelerated theta burst stimulation (aTBS) in patients with Major Depressive Disorder resistant to pharmacological treatment(MDD) in an open label design.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Theta burst stimulation (TBS) is a newer form of rTMS which requires less stimulation time and produces longer lasting post-stimulation effects in the cerebral cortex (4). It has been shown to be effective in inducing synaptic plasticity and has similar or better efficacy in treating depression compared to rTMS (4).Newer accelerated TBS (aTBS) protocols that condense stimulation sessions down to several days rather than weeks have shown similar response rates when compared to prolonged TBS protocols, also with similar tolerability and safety. In order to develop aTBS as an effective treatment for MDD, future research should focus on identification of reliable predictors for better outcome to TBS. The main objectives were: 1) To directly compare multiple different brain-based measures (neuroimaging and electrophysiology) to identify which has the most power in accurately predicting response to TBS compared to sham. 2) To track both short and long-term longitudinal electrophysiological (EEG) changes related to the therapeutic effects of TBS.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • Recruiting
        • University of Calgary

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Participant must meet the DSM-5 diagnostic criteria for single-episode Major Depressive Disorder (MDD).
  2. Participant must have failed to respond to >1 but <4 classes of oral antidepressant treatments in the current episode of depression.
  3. Participant must have a HAMD total score of at least 18

Exclusion Criteria:

  1. The participant's depressive symptoms have previously demonstrated nonresponse to:

    • An adequate course of rTMS/TBS over DLPFC in the current major depressive episode, defined as at least 3 weeks of treatment, 5 times weekly
    • An adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT.
  2. Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression.
  3. Participant has a current or prior DSM-5 diagnosis of Axis I comorbidities, including psychosis, bipolar disorder, obsessive compulsive disorder, based upon clinical assessment and confirmed by the MINI.
  4. Participant has a current or prior DSM-5 diagnosis of Axis II comorbidities, including severe borderline personality disorders, antisocial, schizotypal, schizoid personality disorders based upon clinical assessment and confirmed by the MINI.
  5. Participant has severe suicidal ideation/plan/ intent.
  6. Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria.
  7. Participant has a current or past history of seizures and neurological problems, e.g. head injury, stroke, progressive neurological disorder and complicated and unstable medical disorders, e.g. cardiovascular-related conditions, diabetes.

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active TBS-DLPFC
There is only one arm. All participants will receive Theta Burst Stimulation (transcranial magnetic stimulation) of the dorsolateral prefrontal cortex.
Device: Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

Participants will receive bilateral TBS, 5 times daily (15 minutes between), over 5 consecutive days (25 sessions total). In each session they will receive intermittent TBS (iTBS) over left dorsolateral prefrontal cortex (DLPFC), followed by continuous TBS (cTBS) over right DLPFC. Stimulation sites will be targeted with the Localite neuronavigation system and Visor2 software, and according to Talairach coordinates in relation to individual MRIs. Intensity will be standardized at 120% of RMT.

The MagPro stimulator will deliver iTBS over left DLPFC with 1620 pulses in 54 triplet bursts (5Hz) with train duration of 2 seconds, and intertrain interval of 8 seconds. cTBS over right DLPFC will consist of 1620 pulses in 54 triplet bursts, train duration of 2 seconds, with no intertrain interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Depression Rating Scale
Time Frame: Change from baseline at 5 days of TBS treatment
Clinician administered questionnaire to asses clinical improvement and classify response and remission
Change from baseline at 5 days of TBS treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1. Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: Change from baseline at 5 days of TBS treatment
A ten item clinician administered questionnaire to measure the severity of depressive symptoms on a 0 to 6 severity scale with higher scores indicating more severe depressive symptoms. Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.
Change from baseline at 5 days of TBS treatment
2. Hamilton Anxiety rating Scale (HAM-A)
Time Frame: Change from baseline at 5 days of TBS treatment
A rating scale to measure the severity of anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Change from baseline at 5 days of TBS treatment
2. Columbia Suicide Severity Rating Scale ( CSSRS)
Time Frame: Change from baseline at 5 days of TBS treatment
A suicidal rating scale devised by researchers at Columbia University. The presence of suicidal ideation score ranges from 1-5 and the intensity of the suicidal ideation ranges from 0-25 with higher scores indicating higher levels of intensity.
Change from baseline at 5 days of TBS treatment
MGH Rumination questionnaire
Time Frame: Change from baseline at 5 days of TBS treatment
Self administered 9 items scale to measure the severity of rumination. Each item is measured from 0-4 with a total score range of 0-36. Higher scores indicate more severe rumination.
Change from baseline at 5 days of TBS treatment
Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)
Time Frame: Change from baseline at 5 days of TBS treatment
This is to evaluate the ability to enjoy/experience pleasure. Each item can score 0 or 1 with a total score possibility of 0-14. Higher scores represent higher anhedonia and 3 or over is considered abnormal.
Change from baseline at 5 days of TBS treatment
36 item short form survey (SF-36)
Time Frame: Change from baseline at 5 days of TBS treatment
This is to evaluate physical and emotional health.
Change from baseline at 5 days of TBS treatment
Global Assessment of Functioning (GAF)
Time Frame: Change from baseline at 5 days of TBS treatment
This is to evaluate psychological, social and occupational functioning
Change from baseline at 5 days of TBS treatment
Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)
Time Frame: Pretreatment baseline
Temporal correlation of brain signals as measured by BOLD signals
Pretreatment baseline
Magnetic resonance spectroscopy (MRS)
Time Frame: Pretreatment baseline
To measure glutathione and glutamate concentration in DLPFC and ACC
Pretreatment baseline
Electroencephalogram
Time Frame: Change from baseline at 5 days of TBS treatment
To measure neuronal oscillations
Change from baseline at 5 days of TBS treatment

Collaborators and Investigators

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

Sponsor

University of Calgary

Investigators

  • Principal Investigator: Rajamannar Ramasubbu, MD,FRCPC,MSc, University of Calgary, Department of Psychiatry

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 6, 2018

Primary Completion (Anticipated)

July 1, 2019

Study Completion (Anticipated)

July 1, 2019

Study Registration Dates

First Submitted

July 4, 2018

First Submitted That Met QC Criteria

August 7, 2018

First Posted (Actual)

August 10, 2018

Study Record Updates

Last Update Posted (Actual)

August 10, 2018

Last Update Submitted That Met QC Criteria

August 7, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10001858
  • RT # 10016954 (Other Identifier: University of Calgary)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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