EVALUATION OF LOW EMISSION NEOSYNC EEG SYNCHRONIZED TMS TECHNOLOGY FOR THE TREATMENT OF MAJOR DEPRESSIVE DISORDER: A MULTICENTER RANDOMIZED, DOUBLE-BLIND, SHAM-CONTROLLED, TRIAL
Double Blind Phase:
This is a multicenter study in which 230 subjects will be treated 5 days per week for 6 weeks.
Schedule of visits
After signing informed consent, subjects who qualify for enrollment will discontinue use of their current antidepressant treatment (if applicable). Subjects must have discontinued the antidepressant medication a minimum of 1 week prior to initiation of treatment with the sTMS or sham device. Following wash-out of the antidepressant medication, an additional evaluation will be performed to determine whether the protocol eligibility criteria are met before randomization and treatment.
Qualified subjects will be randomized to either sTMS or sham treatment groups. Treatment will be initiated on Day 1 of the study. Subjects will come to the clinic for 5 daily treatment sessions for a total of 6 and amp;quot;treatment and amp;quot; weeks. A visit interval of 5-10 calendar days has been set for each and amp;quot;treatment and amp;quot; week. Treatment will be discontinued at the end of Week 6 (30 treatment sessions). Subjects will be clinically evaluated for safety and efficacy at the end of each of the six weekly treatment courses. At the end of Week 6, subject will have completed the study treatments and will be offered alternate antidepressant treatment as clinically indicated.Subjects will be asked to return for one follow up visit four weeks after their last sTMS treatment (Week 10) for evaluation and study completion.
Ttreatment plan for the subject during the 4 week follow-up phase:
If the subject does not reach remission by the time of their week 6 evaluation visit, they are eligible to be considered for 4 weeks of open label sTMS treatment during the follow-up phase.
Primary Efficacy Outcome
The primary endpoint will be measured as the mean HAM-D17 total score change from Baseline (Day 0) to Week 6 and compared between the active treatment and sham-controlled groups.
Additional Efficacy Outcomes
Additional outcomes will include the following:
The change in symptom score on the MADRS through 6 weeks of treatment.
The CGI-S and CGI-I scores through 6 weeks of treatment.
The number of clinical responders defined by 50% reduction on the HAM-D17 total symptom scores through 6 weeks of treatment.
The number of subjects achieving remission as defined by a score on the HAM-D17 ≤ 7.
Changes in the subject rated IDS-SR scale through 6 weeks of treatment.
The QOLI through 6 weeks of treatment.
Computerized neuropsychological tests.
Safety will be assessed by the following:
The incidence and severity of all adverse events (including, but not limited to, serious adverse events and non-related adverse events).
Changes in vital signs and weight.
Changes in C-SSRS.
Open label phase:
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.Those subjects who participate in the optional sTMS open label follow-up phase will receive 4 weeks (20 treatments) of sTMS therapy. The treatment is administered for 30 minutes per day, 5 days per treatment week, for 4 treatment weeks. A treatment week is defined as a 5-10 calendar day interval. Each subject who completes the open label follow-up phase of the trial will have a total of 20 treatments within 28-40 calendar days. At minimum, subjects will be asked to return for one follow -up visit four
1.All subjects will be 22- 65 years of age.
2.Major Depressive Episode Diagnosis, Severity, and Duration:
a.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).
b.HAM-D17 score > 17 and Item 1 score greater than or equal to 2.
c.Duration of current episode equal or greater than 8 weeks; the definition of an episode is demarcated by a period of equal or greater than 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.
4.The baseline EEG is of sufficient duration and quality that it can be processed for quantitative analysis.
5.Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.
Open Label Protocol:
Patients who have not reached remission (defined as HAM-D17 ≤ 7) may be offered 4 weeks of open label sTMS treatment
Patients who agree to adhere to treatments schedule