Clinical trial NCT03626181: Biomarkers of Theta Burst Stimulation in Major Depressive Disorder
Official title: Using Multiple Brain-based Biomarkers to Validate and Predict Response to Theta Burst Stimulation as a New Treatment for Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depressive Disorder, Treatment-Resistant
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label study
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: Change from baseline at 5 days of TBS treatment
Secondary outcomes:
measure: 1. Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: 2. Hamilton Anxiety rating Scale (HAM-A)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: 2. Columbia Suicide Severity Rating Scale ( CSSRS)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: MGH Rumination questionnaire
timeFrame: Change from baseline at 5 days of TBS treatment
measure: Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: 36 item short form survey (SF-36)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: Global Assessment of Functioning (GAF)
timeFrame: Change from baseline at 5 days of TBS treatment
measure: Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)
timeFrame: Pretreatment baseline
measure: Magnetic resonance spectroscopy (MRS)
timeFrame: Pretreatment baseline
measure: Electroencephalogram
timeFrame: Change from baseline at 5 days of TBS treatment
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary, Department of Psychiatry
name: Rajamannar Ramasubbu, MD,FRCPC,MSc
role: PRINCIPAL_INVESTIGATOR
References:
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