Triple-blind Randomized Trial Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 210
- 试验地点
- 2
- 主要终点
- Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
This study is a two-arm triple-blind randomized parallel assignment clinical trial as neither the participant, care provider, nor the outcomes assessor know the arm (or condition) assigned to the participants. There are two treatment "arms" in which half will receive fMRI navigated iTBS and the other half will receive neuronavigated iTBS determined by a study randomizer software.
Master randomization list of treatment blinding will be kept by a scientist of the research centre that is not involved in the research project. This can be broken in case of emergency and they can then inform required medical professionals directly if necessary. Directly involved research staff will be blinded (including the PI).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For inclusion in the study, participants must fulfill all the following criteria:
- •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),
- •depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode,
- •moderate symptoms in the current depressive episode as indexed by a score of at least 15 on the Grid 17-item Hamilton Rating Scale for Depression (Grid HRSD-17),
- •have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment,
- •are able to adhere to treatment schedule,
- •have stable psychotropic medications (including prescribed cannabis) or psychotherapy regimen for at least four weeks prior to entering the trial,
- •have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if they are aged ≥ 65.
排除标准
- •Participants fulfilling any of the following criteria will be excluded from the study:
- •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),
- •organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician
- •acute suicidality or threat to life from self-neglect,
- •are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment (pregnancy will be assessed by a urine test),
- •have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker),
- •unwilling to maintain current antidepressant regimen,
- •are taking more than 1 mg of lorazepam per day or equivalent,
- •any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study,
- •any contraindications for MRI
- •have failed a course of ECT within the current depressive episode due to the lower likelihood of response to rTMS (if they have had failed ECT in the past, this does not exclude them)
结局指标
主要结局
Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response.
时间窗: 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).
次要结局
- 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).])
- 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).])
- Change in perceived stress as measures with Perceived stress scale (PSS)(Administered at baseline before first iTBS treatment and after treatment completion (week 6).)
- 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).])
- 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).])
- 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).)
- 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)
- 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.)
- 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).)
- Change in self-reported sleep patterns as measured by Pittsburgh Sleep Quality Index (PSQI)(Before the first iTBS and after treatment (6 weeks).)
- 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.)
- 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).])
- 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).)
- 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)
- 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).)
研究者
Sara Tremblay
Principal Investigator
The Royal Ottawa Mental Health Centre