Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

Not Applicable

• Conditions: Depressive Disorder, Treatment-Resistant
• Interventions: Device: Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

• Registration Number: NCT03626181
• Lead Sponsor: University of Calgary

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-07-04
• Study Start: 2018-07-06
• Status Verified: 2018-08
• Study First Submitted QC: 2018-08-07
• Last Update Submitted: 2018-08-07
• Study First Posted: 2018-08-10
• Last Update Posted: 2018-08-10
• Primary Completion: 2019-07-01
• Study Completion: 2019-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Active TBS-DLPFC	Theta Burst Stimulation ( Transcranial Magnetic Stimulation)	There is only one arm. All participants will receive Theta Burst Stimulation (transcranial magnetic stimulation) of the dorsolateral prefrontal cortex.

Primary Outcome Measures

Name	Time	Method
Hamilton Depression Rating Scale	Change from baseline at 5 days of TBS treatment	Clinician administered questionnaire to asses clinical improvement and classify response and remission

Secondary Outcome Measures

Name	Time	Method
Global Assessment of Functioning (GAF)	Change from baseline at 5 days of TBS treatment	This is to evaluate psychological, social and occupational functioning
Resting state functional connectivity-Functional magnetic resonance imaging (rsfMRI)	Pretreatment baseline	Temporal correlation of brain signals as measured by BOLD signals
1. Montgomery-Åsberg Depression Rating Scale (MADRS)	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.
MGH Rumination questionnaire	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.
Snaith-Hamilton Pleasure scale-Clinician administered (SHAP-C)	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.
36 item short form survey (SF-36)	Change from baseline at 5 days of TBS treatment	This is to evaluate physical and emotional health.
Magnetic resonance spectroscopy (MRS)	Pretreatment baseline	To measure glutathione and glutamate concentration in DLPFC and ACC
Electroencephalogram	Change from baseline at 5 days of TBS treatment	To measure neuronal oscillations
2. Hamilton Anxiety rating Scale (HAM-A)	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.
2. Columbia Suicide Severity Rating Scale ( CSSRS)	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.

Trial Locations

Locations (1)

University of Calgary; 🇨🇦 Calgary, Alberta, Canada