Study of a Repetitive Transcranial Magnetic Stimulation (rTMS) Device for the Treatment of Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 3

Summary: 
      This trial will test the safety and efficacy of a rTMS device for the treatment of major
      depressive disorder (MDD). It is hypothesized that rTMS will have an antidepressant effect.

      It is a 10-week, randomized, sham-controlled, multicenter trial in outpatients recruited in
      both academic and private research centers. It is comprised of three major phases: pre-study
      screening, acute treatment, and post-treatment taper. Eligible patients will be randomized to
      one of two rTMS treatment groups. One group will receive active rTMS treatment and one will
      receive an inactive, or sham, treatment. Each treatment takes about 45 minutes and is done on
      an outpatient basis. All trial related medical care is provided at no cost to the
      participant.
    

Detailed description: 
      This trial will test the safety and efficacy of a rTMS device for the treatment of major
      depressive disorder.

      Major depression is one of the most prevalent and profoundly debilitating diseases worldwide.
      In a recent report, it is estimated that by the year 2020, depression will be second only to
      heart disease in magnitude of disease burden as determined by disability-adjusted life years.

      Despite major advances in the treatment of depression in the last three decades, further
      improvements are needed. For instance, with respect to antidepressant pharmacotherapy, only
      1/3 of patients are estimated to have a nearly full resolution of their clinical symptoms
      with their first medication trial. Indeed, partial remission or lack of response to treatment
      is experienced by the majority of patients. Even with serial trials of antidepressant
      medication, at least 10 to 15% of patients with major depression are estimated to experience
      limited benefit and remain chronically depressed with significant psychosocial morbidity.
      Some patients cannot tolerate the dosage and duration of antidepressant treatments required
      for treatment trials to be considered adequate. In such patients, intolerance of somatic
      treatments for major depression leads to chronicity and impaired function, and likely hinders
      long-term compliance with treatments. For many patients with treatment resistant depression
      (TRD), more complex regimens of polypharmacotherapy, or the use of electroconvulsive therapy
      (ECT) are the only currently available treatment options.

      Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative to treatments
      such as ECT or pharmacotherapy for patients presenting with MDD. An rTMS procedure is
      non-invasive, does not require anesthesia, and may be delivered in an appropriately staffed
      outpatient setting.

      By creating a time-varying magnetic field that is unimpeded by the scalp and skull, TMS can
      focally and painlessly stimulate the cortex of awake individuals. Through the principle of
      magnetic induction, the localized pulsed magnetic field generated in the coil at the surface
      of the head induces an electrical current that depolarizes underlying superficial neurons. It
      is widely thought that rTMS produces its behavioral effects solely through the induction of
      current flow in cortex.

      Several factors have driven the investigation of rTMS for the treatment of MDD. Early reports
      of changes in mood in normal participants, the non-invasive nature of rTMS, the favorable
      side effect profile compared to ECT, and the non-response of a number of MDD patients to
      pharmacotherapy and/or ECT, all have likely played a role. Since the initial studies, there
      has continued to be high interest in rTMS as an antidepressant treatment. Multiple trials
      have been conducted from researchers in diverse environments around the world. However, until
      now, there have been no rigorously conducted large, multicenter rTMS clinical trials in the
      treatment of patients with MDD. Because the published research has largely been conducted in
      single centers, the sample sizes in these antidepressant trials have been small. However, the
      majority of more than 20 reports have found modest to large antidepressant effects that
      increase over the trial period. By design, this trial will provide more robust information
      regarding the antidepressant effect of rTMS in the adult population of MDD patients.
    

Intervention name(s): Repetitive Transcranial Magnetic Stimulation
Intervention type(s): Device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Major Depressive Disorder; Repetitive Transcranial Magnetic Stimulation; rTMS; Non-invasive Neuromodulation; Antidepressant