Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Royal Ottawa Mental Health Centre
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
voluntary and competent to consent to study,
Adults aged 18 years old or older,
can speak and read English,
primary and/or predominant diagnosis of major depressive episode without psychotic features in the current episode (confirmed by a Mini-International Neuropsychiatric Interview),
Disqualifiers
diagnosis of bipolar I or II disorder, based on the DSM-5 criteria
current or past (< 3 months) substance (excluding caffeine or nicotine) or alcohol use disorder, as defined in DSM-5 criteria. Based on the DSM-5 criteria, mild cannabis or alcohol use disorder would be permissible in the past 3 months, moderate to severe would be an exclusion.
current use of illegal substances or cannabis (unless medical use, see note below), confirmed by urine drug screen
have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction),
Trial design
Design model
Parallel
Treatments tested in this trial
repetitive Transcranial Magnetic Stimulation
DeviceRepetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Typical treatments involve 30 to 45 minutes daily sessions delivered over 4 to 6 weeks. Recent technical advances allowed the development of theta burst stimulation (TBS), a novel rTMS paradigm that reduces daily sessions to 3 to 4 minutes while maintaining the same clinical efficacy. This study will specifically be administering intermittent TBS (iTBS), which is a novel refinement of conventional rTMS and consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz).
Treatment groups
210 Participants
are divided into 2 treatment groupsGroup A: fMRI guided iTBS targettingExperimental treatment 1 intervention
Group B: Neuronavigation guided iTBS targettingActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response.
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).
Time frame
Administered at baseline (prior to first iTBS treatment) and every 2 weeks after that for 6 weeks (week 2, week 4, and week 6).Secondary outcomes
1
Change in severity of clinician-rated depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 52 (worst outcome, extreme depression).
Time frame
Administered at screening, before the first iTBS, week 2, week 4 and after iTBS treatment (week 6).2
Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II).
As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme depression).
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).]3
Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI)
As a secondary measure of anxiety symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme anxiety).
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).]4
Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS).
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).
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).]Other outcomes
1
Incidence of Treatment-Emergent Adverse Events
Adverse events will be tracked and recorded.
Time frame
Daily Monday-Friday throughout study (6 weeks).2
Side Effects
Side effects will be tracked and recorded on any TMS visits, using the TMS side effects questionnaire.
Time frame
Daily Monday-Friday throughout study (6 weeks).Sponsors and contacts
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Source ClinicalTrials.gov