Neuromarkers Identification in Major Depressive Disorder Based on Monitoring Measures

Study Overview
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Brief Summary
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The investigators propose a multi-source pattern which integrates neuroimaging data associated with multiple, symptom-related neural processes relevant in depression to improve classification accuracy. The investigators conclude that combining brain activation related to the core-symptoms of depression using the multi-source monitoring data substantially increases classification accuracy while providing a sparse relational neuromarkers-model for future prediction.

Detailed Description
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The Multiway stimulator coil® (Brainsway Ltd.) is a novel TMS stimulator with several new and unique properties. Currently standard TMS devices include a single channel, and can operate only a single coil. The Multiway stimulator coil® (Brainsway Ltd.) includes two channels which can operate two independent TMS coils, either simultaneously or sequentially. The Multiway stimulator coil® (Brainsway Ltd.) may be used to obtain a differential activation of various brain regions. For instance it can be used to induce high frequency stimulation of a certain brain region, thus inducing facilitation, while simultaneously stimulate at low frequency in another brain region, leading to inhibition. In the current study the investigators propose a multi-source pattern which integrates neuroimaging data associated with multiple, symptom-related neural processes relevant in depression to improve classification accuracy. The investigators conclude that combining brain activation related to the core-symptoms of depression using the multi-source monitoring data substantially increases classification accuracy while providing a sparse relational neuromarkers-model for future prediction. The purpose of the study is to to monitor and optimize the anti depressive effect of brain modulation technique using novel multi model monitoring approach. Subjects will be treated with one of two designs of the study device (the Multiway Coil®): Single Channel with a coil placed over the left PFC (10 Hz). Two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC. All subjects in the current study will undergo monitoring procedure inclusive of functional MRI and electroencephalogram.

Official Title
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Identification of Neuromarkers in Novel Neuromodulation Treatment in Major Depressive Disorder Based on Integration of Multiple Monitoring Measures

Conditions
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Depression

Intervention / Treatment
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* Device: single channel Multiway Coil®
* Device: Two channels Multiway stimulator coil® (Brainsway Ltd.)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient Diagnosed by senior psychiatrist as suffering from major depression episode according to DSM IV using the Structured Clinical Interview for DSM-4 (SCID). Rating on HDRS-21>20. Age: 18-68 years. Treated for the current depressive episode, at least four weeks, with at least one antidepressant in accepted dose, without improvement, according to their medical chart and ATHF ( antidepressant treatment history form) instruction guidelines . Gave informed consent for participation in the study. Negative answers on safety screening questionnaire for transcranial magnetic stimulation. Exclusion Criteria: Diagnosis as suffering from other diagnosis on axis 1 ( like: schizophrenia, bipolar disorder, psychotic depression, geriatric depression). Diagnosis as suffering from Severe Borderline Personality Disorder or hospitalized due to exacerbation related to of borderline personality disorder. Substantial suicidal risk as judged by the treating psychiatrist. Attempted suicide in the past year. Any current unstable medical or surgical illness. History of seizure or heat convulsion. History of epilepsy or seizure in first degree relatives. History of head injury. History of any metal in the head (outside the mouth). Known history of any metallic particles in the eye, implanted cardiac pacemaker or any intracardiac lines, implanted neurostimulators, surgical clips, cochlear implants or any medical pumps. History of hearing loss. History of drug abuse or alcoholism in the last 6 month. Pregnancy or not using a reliable method of birth control. Systematic and metabolic unstable disorders. Inadequate communication with the patient. Under custodial care. Participation in current clinical study or clinical study within 30 days prior to this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: single channel<br> | Device: single channel Multiway Coil®<br>* During the single channel treatment trial period the patients will receive the following dose of rTMS: 10 Hz - left DLPFC ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks).<br>|
| Experimental: Two channels Multiway stimulator coil® (Brainsway Ltd.)<br> | Device: Two channels Multiway stimulator coil® (Brainsway Ltd.)<br>* During the two channels treatment trial period the patients will receive the following dose of rTMS: 10 Hz- left DLPFC, 1Hz - right DLPFC together. 10 Hz protocol: ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks) 1 Hz protocol: 1 Hz, at 120% MT, 5 min pulse train, 1 min inter-train interval, 6 trains, i.e. a total of 1800 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 36,000 pulses in 4 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical antidepressant response as defined by decline of HDRS-21 score over time | Clinical antidepressant response at the end of the treatment, defined as a decline in Hamilton depression rating scale (HDRS-21) from the baseline rating by 50%. | 20 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic improvement | Symptomatic improvement at the 4-week end point as measured with Hamilton Anxiety Rating Scale ( HARS) | day 20 | 
| Clinical antidepressant remission as defined by decline of HDRS-21 score over time | Clinical antidepressant remission at the end of the treatment, defined as exit Hamilton Depression Rating Scale <10. | Day 20 | 
| Symptomatic improvement | Symptomatic improvement at the 4-week end point as measured with Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | day 20 | 
| Symptomatic improvement | Symptomatic improvement at the 4-week end point as measured with Clinical Global Impression (CGI) | day 20 |