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Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT03626181
Recruitment Status : Unknown
Verified August 2018 by Rajamannar Ramasubbu, University of Calgary.
Recruitment status was:  Recruiting
First Posted : August 10, 2018
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
Rajamannar Ramasubbu, University of Calgary

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Treatment-Resistant Device: Theta Burst Stimulation ( Transcranial Magnetic Stimulation) Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Using Multiple Brain-based Biomarkers to Validate and Predict Response to Theta Burst Stimulation as a New Treatment for Major Depressive Disorder
Actual Study Start Date : July 6, 2018
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : July 1, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI) [ Time Frame: Pretreatment baseline ]
    Temporal correlation of brain signals as measured by BOLD signals

  9. Magnetic resonance spectroscopy (MRS) [ Time Frame: Pretreatment baseline ]
    To measure glutathione and glutamate concentration in DLPFC and ACC

  10. Electroencephalogram [ Time Frame: Change from baseline at 5 days of TBS treatment ]
    To measure neuronal oscillations


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
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): NCT03626181


Contacts
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Contact: Rajamannar Ramasubbu, MD,FRCPC,MSc 403-210-6890 rramasub@ucalgary.ca
Contact: Laina B McAusland, RN,MSc 403-210-6905 lbsorens@ucalgary.ca

Locations
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Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 4Z6
Sponsors and Collaborators
University of Calgary
Investigators
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Principal Investigator: Rajamannar Ramasubbu, MD,FRCPC,MSc University of Calgary, Department of Psychiatry
More Information
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Publications of Results:

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Responsible Party: Rajamannar Ramasubbu, Professor, University of Calgary
ClinicalTrials.gov Identifier: NCT03626181    
Other Study ID Numbers: 10001858
RT # 10016954 ( Other Identifier: University of Calgary )
First Posted: August 10, 2018    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 2018

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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
Additional relevant MeSH terms:
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Depressive Disorder
Depression
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
 Mood Disorders
Mental Disorders
Behavioral Symptoms