The goal of this clinical trial is to estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements.
Techniques for modulating human brain networks are rapidly evolving. One of the most exciting new developments is accelerated intermittent theta burst stimulation (aiTBS), a transcranial magnetic stimulation (TMS) protocol that involves multiple daily treatments rather than gold standard once daily treatment. A specific accelerated iTBS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was cleared by the FDA in September 2022 based on two pilot studies in which patients with treatment-resistant depression rapidly and robustly improved with SAINT. Many of these patients had been depressed for decades and had not improved with conventional TMS or electroconvulsive therapy. Despite these promising results, two issues may limit SAINT scalability: 1) SAINT has only been tested at a single site in a small number of patients, 2) SAINT has never been tested without individualized resting state functional connectivity (rsfc) targeting, which is not widely available or covered by insurance. In this pilot trial, patients with treatment-resistant depression (n=40) will be randomized to one of two active treatment arms: 1) Real aiTBS with real individualized rsfc targeting, or 2) Real aiTBS with sham individualized rsfc targeting (i.e. conventional TMS targeting based on scalp landmarks). All patients will receive active stimulation, which will facilitate enrollment and reduce ethical concerns about placebo treatment in a vulnerable population when there is existing evidence of treatment efficacy. Patients and clinicians will be blind to group assignment, and blind integrity will be assessed. All patients will undergo MRI scans immediately before treatment and at one month follow up, which aligns with our clinical outcome measures.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
40
Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise. This protocol will be modeled after the FDA cleared Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, but the patented SAINT rsfc targeting algorithm will not be used for either arm.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size (i.e., Cohen's d) of imaging-guided accelerated TMS relative to scalp-targeted TMS. This outcome has not changed since the original grant application for this study. Actual group differences will be explored in a secondary analysis of this primary outcome measure. Note added May 2025: The description of the primary outcome measure was clarified. The primary outcome remains unchanged.
Time frame: one month after treatment
Montgomery-Åsberg Depression Rating Scale (MADRS)
Depression severity rating scale (0-60, higher numbers indicate higher severity). The primary analysis of the primary outcome will be the effect size of imaging-guided accelerated TMS relative to scalp-targeted TMS. In other words, the "number needed to scan." This outcome has not changed since the original grant application for this study and the data remain blinded at the time of this clarification. Actual group differences will be explored in a secondary analysis of this primary outcome measure.
Time frame: immediately after treatment ends
Beck Depression Inventory (BDI)
Depression severity rating scales (0-63, higher numbers indicate higher severity)
Time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
Quick Inventory of Depressive Symptomatology (QIDS)
Depression severity rating scales (0-27, higher numbers indicate higher severity)
Time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
Change in resting state functional connectivity in the depression network
blood oxygen level-dependent (BOLD) signal
Time frame: one month after treatment
Percentage of screened patients from TMS clinical programs who select the accelerated iTBS trial over routine clinical TMS
Patient preference measure
Time frame: through study completion, an average of 2 years
Temperament and Character Inventory, Revised 140-item
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
Time frame: one month after treatment
Emotional Conflict Resolution Task
Computer task measuring accuracy and reaction time
Time frame: one month after treatment
Learning, Multi-Source Interference Task (MSIT)
Computer task measuring accuracy and reaction time
Time frame: one month after treatment
Penn Emotion Recognition Task (ER-40)
Computer task measuring accuracy and reaction time
Time frame: one month after treatment
Death Suicide IAT (DSIAT)
Computer task measuring reaction time
Time frame: one month after treatment
Beck Anxiety Inventory (BAI)
Anxiety severity rating scale (0-63, higher numbers indicate higher severity)
Time frame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.