Evaluation of the Brainsway Deep Transcranial Magnetic Stimulation (TMS) H-Coil in the Treatment of Major Depression Disorder

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of deep brain rTMS, (Transcranial Magnetic Stimulation), a new experimental procedure using the H-Coil, in subjects with Major Depressive Disorder that have been previously unsuccessfully treated with antidepressant medications.

Detailed Description
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This study is a multicenter, randomized double blind, sham controlled study to evaluate the safety and efficacy of H-coil deep transcranial magnetic stimulation (dTMS) as a treatment for patients with major depressive disorder who have been previously unsuccessfully treated with antidepressant medications. Studies of repetitive transcranial magnetic stimulation (rTMS), typically using a figure-8 coil, have shown that stimulating superficial brain regions can be beneficial in treating major depression. Differing from traditional figure-8 coil, the H-coil is designed to stimulate deep brain regions related to motivation, reward, and pleasure. Preliminary studies have been conducted and seem to indicate that through stimulating certain brain areas with the H-coil, dTMS may have an antidepressant effect. The study population will consist of patients with major depressive disorder who have failed adequate medication treatment or shown significant intolerance to medications. The study duration is 18 weeks, with a 2 week period of weaning the patient off medication, followed by 4 weeks of 5 daily treatments and 12 weeks of biweekly treatments. Mood and mental state will be carefully monitored through standard psychological scales and rating during the drug taper-down and throughout treatment.

Official Title
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A Prospective Multicenter Double Blind Randomized Controlled Trial to Explore the Tolerability, Safety and Efficacy of the H-Coil Deep Transcranial Magnetic Stimulation (TMS) in Subjects With Major Depression Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Brainsway H-Coil Deep TMS System
* Device: Brainsway H-Coil Deep TMS System (Sham treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients. Men and women 22-68 years of age. Primary DSM-IV diagnosis of Major Depression, single or recurrent episode. Current depressive episode is less than 5 years duration. The patient did not respond to at least one but not more than four antidepressant treatments in the current episode. Patients who have not completed antidepressant trials due to intolerance to therapy of 2 or more anti-depressant medications in the current episode. Satisfactory safety screening questionnaire for transcranial magnetic stimulation. Patients not suffering from hypo or hyper-thyroidism based on pre-study TSH level or medically stabilized. Patients able to tolerate psychotropic medication washout and no psychotropics during the treatment, other than benzodiazepine at equivalent daily dose of up to 3 mg lorazepam. Exclusion Criteria: A history of schizophrenia, any psychotic disorder, PTSD, bipolar disorder, OCD, eating disorders (e.g., anorexia nervosa, bulimia) or substance abuse A history of panic disorder, social anxiety disorder or personality disorder (such as antisocial, schizotypal, histrionic, borderline, narcissistic) as assessed by the investigator to be primary, causing a higher degree of distress or impairment than MDD. A history of any significant medical disease (i.e., cardiovascular, gastrointestinal, etc.) A history of seizures, at risk for seizure (e.g., history of significant head trauma with loss of consciousness for greater than or equal to 5 minutes or familial or personal history of epilepsy) or have been diagnosed with a seizure disorder. Undergone rTMS treatment, Vagus Nerve Stimulation, or Deep Brain Stimulation. Received ECT within the last 3 months or failed to respond to ECT treatment. Individuals with a significant neurological disorder or insult including: Any condition likely to be associated with increased intracranial pressure Space occupying brain lesion Any history of seizure EXCEPT those therapeutically induced by ECT History of cerebrovascular accident Transient ischemic attack within two years Cerebral aneurysm Dementia Parkinson's disease Huntington's chorea Multiple sclerosis Individuals with hearing loss. Any intracranial implant such as aneurysm clips, shunts, stimulators, cochlear implants, or electrodes, or any other metal object within or near the head, excluding the mouth, that cannot be safely removed. A cardiac pacemaker, implanted medication pump, intracardiac line, or acute, unstable cardiac disease. Use of fluoxetine within 6 weeks of the randomization visit. Use of a Monoamine Oxidase Inhibitor (MAOI) within 2 weeks of the randomization visit. Present suicidal risk as assessed by the investigator. Implanted neurostimulators. History of abnormal MRI. If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the rTMS trial. Clinically significant laboratory abnormality, in the opinion of the Investigator based on CBC and biochemistry. Women of childbearing potential and not using a medically accepted form of contraception when engaging in sexual intercourse. Women: if pregnant, planning on becoming pregnant, or currently nursing.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham<br>Sham treatment | Device: Brainsway H-Coil Deep TMS System (Sham treatment)<br>* In the sham treatment,the electrical field induced by the sham coil cannot invoke any action potentials and if no action potentials are induced, then the electric field is insignificant and there is no treatment effect on the brain.<br>|
| Active Comparator: Active<br>Active Deep Transcranial Magnetic Stimulation treatment | Device: Brainsway H-Coil Deep TMS System<br>* Deep Transcranial Magnetic Stimulation (DTMS) is a new form of TMS which allows direct stimulation of deeper neuronal pathways than the standard TMS. The H-coil is a novel DTMS coil designed to allow deeper brain stimulation without a significant increase of electric fields induced in superficial cortical regions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDRS-21 |  | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 5 weeks | 
| Remission rates |  | 5 weeks | 
| Quality of Life |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, Transcranial Magnetic Stimulation, MDD, Major Depressive Disorder