The primary objective of this study is to demonstrate the preliminary effectiveness, tolerability, and feasibility of an accelerated, intermittent theta burst stimulation (iTBS) protocol for adults diagnosed with Major Depressive Disorder who are currently experiencing a Major Depressive Episode that does not rely on radiological imaging for the individualized targeting of desired treatment location of the dorsolateral prefrontal cortex and that is limited to 36 total treatments.
The study will be performed at a single site, where MDD patients, if eligible, can be consented to participate. Prior to iTBS Stimulation the Motor Threshold (MT) will be established for each subject individually. Each subject will be evaluated for 5 days during their iTBS treatment protocol and at 4 weeks post-treatment. The total study duration is expected to be approximately 8 months depending upon enrollment rate. The study consists of 8 visits. Each subject will be treated with an accelerated iTBS regimen for 5 days. This consists of 6-8 daily treatments which begin at 60-minute intervals for a total of 36 total treatments.
Visit 1 for subject intake with study physician. Visit 2 will consist of the establishment of baseline ratings. During visits 3-7 subjects will receive study protocol iTBS treatments. Visit 8 will be at 4 weeks post-treatment and will consist of administration of assessments. Study visits on treatment days are estimated to take between 5-7 hours depending on the day.
The Beam F3 System will be used to target the desired F3 location of the International 10-20 System. These coordinates are used to triangulate the desired treatment site on each patient on the first day of treatment and are saved for further treatments.
A Neuronetics NeuroStar XPLOR System version 3.6 will be used to deliver iTBS therapy. This consisted of 20 cycles of 5 bursts of 3 pulses at 50 Hz every 200 msec delivered in 2 second trains with an 8 second interval. Treatment sessions will be delivered hourly. Six or Eight sessions will be applied per day (3,600/4,800 pulses/day) for 5 consecutive days (21,600 pulses in total). Stimulation will not exceed 120% rMT.
Evaluations will consist of the Patient Health Questionaire-9 (PHQ-9), Quick Inventory of Depressive Symptomology (QIDS) Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depressive Ratings Scale (HAM-D). The primary endpoint is Change in MADRS scores from baseline to 4 weeks post treatment. Secondary endpoints include changes in the scores of all evaluations from baseline throughout the study. Response and remission rates will be calculated using both the MADRS and HAM-D at both the end of treatment and 4 weeks post study.
Staff handling data are trained in secure handling of Protected Health Information. Multiple layers of physical access will be employed, including individually assigned access cards and locked filing cabinets. Electronic records may be captured on the Sonder Wellness HIPAA compliant EMR database, Sonder Wellness managed and compliant shared network drive with controlled access to research staff, and/or a Sonder Wellness approved and secured external drive. All study data will exclusively use a de-identified code. Participant identifiers and corresponding code will be limited to key documents and maintained separately from the study data. Data will be collected and stored at a single site. Paper data will be stored on-site and electronic data on Sonder Wellness servers. Only Sonder Wellness research staff will have access to identifiable information. Data will be de-identified for affiliate analysis or summary reporting. No specimens will be collected or transported.
A sample size of 20 total subjects was selected as sufficient to perform a preliminary assessment of the effect size. The sample size is not based on formal power requirements for a statistical hypothesis test but is based on a desire to obtain a reasonable initial data set for exploratory and planning purposes.
All statistical analyses will be performed using SAS® version 9.4 (or higher). The full analysis set (FAS) will include all subjects who receive at least thirty treatment sessions. The FAS will be used for analyses of all efficacy outcome measures. The Safety population will include all subjects who receive at least one treatment session. This population will be used for demographic \& Baseline characteristics and Safety outcome measures.
For efficacy endpoints, the Tables, Listings and Figures analysis and reporting will be performed on FAS population. A subject level listing will also be provided for each of these efficacy outcome MADRS, HAM-D, QIDS-16 and PHQ-9 separately presenting total score and each subscale score by different visits.
The primary endpoint of change in MADRS total score from baseline to 4 weeks post treatment will be analyzed using paired t test or Wilcoxon signed rank test. Mean change with the associated standard error and 95% CIs for the change will be presented along with the p-value.
