Synchronized Transcranial Magnetic Stimulation (sTMS) in Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: NEST-1 (NeoSync EEG Synchronized TMS); SHAM
Intervention description: The NeoSync EEG Synchronized TMS (NEST) is an electromechanical medical device that produces and delivers a sinusoidal magnetic field to areas of the brain in the treatment of Major Depressive Disorder.; The sham device is configured to simulate the actual NEST-1 device without sTMS therapy being actively delivered.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 22 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: TMS,; MDD,; Depression,; sTMS,; NEST,; NeoSync,; EEG,; synchronous,; non-invasive neuromodulation,; transcranial magnetic stimulation,; antidepressant,

Summary:

      This study is designed to evaluate the safety and efficacy of synchronized transcranial
      magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects
      with Major Depressive Disorder. This is a multicenter study in which subjects will be
      randomized to receive treatment 5 days per week for 6 weeks. Subjects who complete 6 weeks of
      double-blind treatment may be eligible to receive up to four weeks of open label sTMS therapy
      or antidepressant medications during the follow-up phase of the study. Follow-up evaluation
      visits will be conducted during those four weeks, with the frequency of the visits determined
      by the treatment choice during that timeframe.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major
             Depressive Disorder by DSM-IV-TR criteria rendered by structured interview using the
             Mini International Neuropsychiatric Interview (MINI).

          -  HAM-D17 score >= 17 and Item 1 score greater than or equal to 2.

          -  Duration of current episode >=8 weeks. The definition of an episode is demarcated by a
             period of >=2 months when the subject did not meet full criteria for the DSM-IV-TR
             definition of Major Depressive Episode. Maximum duration of current episode cannot
             exceed 2 years.

          -  The baseline EEG is of sufficient duration and quality that it can be processed for
             quantitative analysis.

          -  Subjects are willing and able to adhere to the intensive treatment schedule and all
             required study visits.

        Exclusion Criteria:

          -  Subjects are unable or unwilling to give informed consent.

          -  Diagnosed with the following conditions (current unless otherwise stated):

               -  Any other current primary Axis I mood, anxiety, or psychotic disorder, including
                  bipolar disorder.

               -  Depression secondary to a general medical condition, or substance-induced.

               -  History of substance abuse or dependence within the past 6 months (except
                  nicotine and caffeine).

               -  Any bipolar disorder or psychotic disorder (lifetime), including schizoaffective
                  disorder, or major depression with psychotic features in this or previous
                  episodes.

               -  Eating disorder (current or within the past year).

               -  Obsessive compulsive disorder (lifetime).

               -  Post-traumatic stress disorder (current or within the past year).

               -  ADHD (currently being treated).

          -  Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR
             criteria, which in the judgment of the Investigator may hinder the subjects in
             completing the procedures required by the study protocol.

          -  Subjects with a clinically defined neurological disorder including, but not limited
             to:

               -  Any condition likely to be associated with increased intracranial pressure.

               -  Space occupying brain lesion.

               -  Any history of seizure EXCEPT those therapeutically induced by ECT (childhood
                  febrile seizures are acceptable and these subjects may be included in the study).

               -  History of stroke.

               -  Transient ischemic attack within two years.

               -  Cerebral aneurysm.

               -  Dementia.

               -  Mini Mental Status Exam (MMSE-2) score of =<24.

               -  Parkinson's disease.

               -  Huntington's disease.

               -  Multiple sclerosis.

               -  Increased risk of seizure for any reason, including prior diagnosis of increased
                  intracranial pressure (such as after large infarctions or trauma), or currently
                  taking medication that lowers the seizure threshold. Medications that lower the
                  seizure threshold are included in the Prohibited Concomitant Medication (Section
                  5.7).

          -  Subjects who are currently hospitalized due to severity of depression symptoms.

          -  Subjects with any of the following treatment histories:

               -  TMS treatment within 6 months prior to the screening visit.

               -  ECT treatment within 1 year prior to the screening visit.

               -  Failure to respond to TMS or ECT treatment (i.e., consistent with ATHF confidence
                  level 3 or higher) in this or any previous episode.

               -  Lifetime history of treatment with Deep Brain Stimulation or Vagus Nerve
                  Stimulation.

               -  Use of any investigational drug or device within 4 weeks of the randomization
                  visit.

               -  Subjects who have been treated with fluoxetine within the past four weeks.

               -  If participating in psychotherapy, must have been in stable treatment for at
                  least 2 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 trial.

               -  Failure to respond to Monoamine Oxidase Inhibitors (MAOIs) in the current
                  episode.

          -  Use of any medication(s) listed on the Prohibited Concomitant Medication within 1 week
             of randomization.

          -  Subjects are adequately benefiting from current antidepressant medication(s).

          -  Significant acute suicide risk, defined as:

               -  Suicide attempt within the previous 6 months that required medical treatment; or

               -  Greater than or equal to 1 suicide attempts in the past 12 months; or

               -  Has a clear-cut plan for suicide and states that he/she cannot guarantee that
                  he/she will call his/her regular psychiatrist or the Investigator if the impulse
                  to implement the plan becomes substantial during the study; or

               -  In the Investigator's opinion, is likely to attempt suicide within the next 6
                  months.

          -  Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable
             cardiac disease.

          -  Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants,
             stents, or electrodes) or any other metal object within or near the head, excluding
             the mouth, which cannot be safely removed.

          -  Clinically significant abnormality or clinically significant unstable medical
             condition, as indicated by medical history, physical examination, ECG results, or
             clinical laboratory testing, that in the Investigator's judgment might pose a
             potential safety risk to the subject or limit interpretation of the trial results,
             e.g., any uncontrolled thyroid disorders, hepatic, cardiac, pulmonary and renal
             malfunctioning.

          -  Women who are currently pregnant or not using a medically acceptable means of birth
             control and women who are breastfeeding.

          -  Positive urine drug screen for illicit substances. (A positive urine drug screen at
             screening may be repeated once prior to randomization).

          -  Any condition which in the judgment of the Investigator would prevent the subject from
             completion of the study.