Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
- Conditions
- Depressive Disorder, MajorDepressionDepressive Episode
- Interventions
- Device: repetitive Transcranial Magnetic Stimulation
- Registration Number
- NCT06152705
- Lead Sponsor
- The Royal Ottawa Mental Health Centre
- Brief Summary
In this triple-blind randomized controlled trial, we ask if targeting intermittent theta burst stimulation (iTBS) based on individual resting state connectivity improves treatment outcomes in major depressive disorder (MDD). For the trial, we will recruit 210 patients with major depressive disorder. Each patient will undergo a 30-40-minute MRI scan, after which they will receive a 6-week standard iTBS treatment. Participants will be randomized to receive iTBS either to the standard neuronavigated target (a technique for treatment location targeting, based on group-average connectivity) or to a personalized connectivity-guided target selected based on individual functional connectivity scans. The main outcome of this trial is response rate as determined by ≥ 50% reduction in Grid HRSD-17 scores. Secondary outcomes include remission rate, change in depression, anxiety and anhedonia symptoms, quality of life, and biological measures of heart rate variability, objective sleep measures and daily activity as a proxy of anhedonia - defined as a reduced ability to experience pleasure.
- Detailed Description
Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved and widely used focal, safe, well-tolerated, and non-invasive brain stimulation method for the treatment of depression, and has been approved in Canada. Typical clinical rTMS is delivered on the left dorsolateral prefrontal cortex (DLPFC) at a 10 Hz frequency over 30-45 minutes to induce an increase in cortical excitability, which outlasts the duration of stimulation. iTBS is a novel refinement of conventional rTMS. iTBS consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz). However, instead of 30 minute treatment sessions, iTBS has comparable clinical efficacy with only 3 minute treatment sessions. Currently roughly 50% of the people receiving rTMS treatment for depression respond to the treatment. One of the main goals of current research in rTMS is to find improvements in the protocol to increase the number of responders.
One of the potential ways to improve rTMS is to select the target based on individual resting state functional connectivity. Within the DLPFC, there are still several possible targets for the rTMS. Functional magnetic resonance imaging (fMRI) studies have shown that therapeutic effects of rTMS are related to its effects on the subgenual anterior cingulate cortex (sgACC; Broadman area 25). Past literature has shown that in MDD the effectiveness of a target is related to its connectivity with the sgACC. A recent study showed in a retrospective sample of MDD patients that response to rTMS correlates with the distance from the personalized connectivity-guided target rather than a group average target, opening the door for individualized connectivity-guided rTMS targeting. Yet, the question whether individualized connectivity-guided rTMS targeting improves rTMS outcomes in a prospective sample has never been investigated. In this two-arm triple-blind randomized parallel assignment clinical trial we will test if 6-week treatment using individualized connectivity-guided iTBS targeting leads to better outcomes in MDD compared to conventional neuronavigated iTBS.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description fMRI guided iTBS targetting repetitive Transcranial Magnetic Stimulation The target selected is based on functional connectivity determined from the MRI scan. Neuronavigation guided iTBS targetting repetitive Transcranial Magnetic Stimulation A technique for treatment location targeting, based on structural images of the brain using standard coordinates.
- Primary Outcome Measures
Name Time Method Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response. Administered at baseline (prior to first iTBS treatment) and every 2 weeks after that for 6 weeks (week 2, week 4, and week 6). Clinical response will be defined as a ≥ 50% reduction in the 17-Item Grid Hamilton Rating Scale for Depression (GRID-HRSD-17). The Grid HRSD is a clinician-rated instrument with seventeen items used to measure the severity of depressive episodes. Remission will be defined as a HRSD-17 score \< 8 after 6 weeks of treatment.
Score scale from 0 (better outcome, no depression thus better clinical response) to 60 (worst outcome, extreme depression thus worse clinical response).
- Secondary Outcome Measures
Name Time Method Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI) Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).] As a secondary measure of anxiety symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme anxiety).
Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II). Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).] As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme depression).
Change in perceived stress as measures with Perceived stress scale (PSS) Administered at baseline before first iTBS treatment and after treatment completion (week 6). To assess the effect of treatment on self-report measures of stress that may be improved by iTBS.
Score scale from 0 (better outcome, no perceived stress) to 40 (worst outcome, extreme perceived stress).Change in self-reported sleep quality as measured by Leeds Sleep Evaluation Questionnaire (LSEQ) Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).] To assess the effect of treatment on self-report sleep that may be improved by iTBS.
Score scale from 0 (better outcome, excellent sleep) to 100 (worst outcome, extremely poor sleep).Change in self-reported anhedonia as measured by Snaith-Hamilton Pleasure Scale (SHAPS) Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).] To assess the effect of treatment on self-report measures of anhedonia symptoms that may be improved by iTBS.
Score scale from 0 (better outcome, no anhedonia) to 14 (worst outcome, extreme anhedonia).Change in severity of clinician-rated depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Administered at screening, before the first iTBS, week 2, week 4 and after iTBS treatment (week 6). As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 52 (worst outcome, extreme depression).
Change in quantity of sleep as measured with Empatica EmbracePlus Smartwatch Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit To assess the effect of treatment on objective measures of sleep patterns that may be improved by iTBS.
Change in motion intensity (based on number of steps and total activity) as measured with Empatica EmbracePlus Smartwatch Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit. To assess the effect of treatment on objective measures of physical activity that may be improved by iTBS.
Change in self-reported hopelessness as measured by Beck Hopelessness Scale (BHS) Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6). To assess the effect of treatment on self-report symptoms of hopelessness that may be improved by iTBS.
Score scale from 0 (better outcome, no sense of hopelessness) to 20 (worst outcome, extreme sense of hopelessness).Change in self-reported sleep patterns as measured by Pittsburgh Sleep Quality Index (PSQI) Before the first iTBS and after treatment (6 weeks). To assess the effect of treatment on self-report sleep that may be improved by iTBS.
Score scale from 0 (better outcome, very high quality sleep) to 21 (worst outcome, very low quality sleep).Change in motion heart rate variability as measured with Empatica EmbracePlus Smartwatch Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit. To assess the effect of treatment on objective measures of heart-rate variability, which has been shown to be linked to MDD and that may be improved by iTBS.
Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS). Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).] To assess the effect of treatment on suicidal thoughts that may be improved by iTBS.
Score scale from 0 (better outcome, no desire for suicide) to 38 (worst outcome, extreme desire for suicide).Change in quality of life as measured with Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Time Frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6). To assess the effect of treatment on self-report measures of quality of life that may be improved by iTBS.
Score scale from 0 (worse outcome, poor life satisfaction and poor life quality) to 70 (better outcome, high life satisfaction and high quality of life).Change in physiological stress based on pulse rate and electrodermal activity response as measured with Empatica EmbracePlus Smartwatch Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit To assess the effect of treatment on objective measures of stress that may be improved by iTBS.
Change in well-being as measured with Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS) Administered before the first iTBS, week 2, week 4 and after iTBS treatment (week 6). To assess the effect of treatment on self-report measures of well-being that may be improved by iTBS.
Score scale from 14 (worse outcome, poor mental wellbeing) to 70 (better outcome, excellent mental well).
Trial Locations
- Locations (1)
The Royal's Institute of Mental Health Research
🇨🇦Ottawa, Ontario, Canada