Canadian rTMS Treatment and Biomarker Network in Depression Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 212
- 试验地点
- 6
- 主要终点
- 17-item Hamilton Rating Scale for Depression (HRSD-17) Change
研究概览
简要总结
Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for medically refractory major depressive disorder (MDD). rTMS involves direct stimulation of cortical neurons using externally applied, powerful, focused magnetic field pulses. Dozens of studies and several meta-analyses over the last 15 years have shown that rTMS of the dorsolateral prefrontal cortex (DLPFC) produces statistically significant improvements in MDD, even when medications have failed. However, other possible targets may also yield improvement in symptoms.
In an attempt to enhance the therapeutic efficacy of current interventions for TRD, attention has turned to identifying domain-specific biomarkers in hopes of ultimately individualizing and predicting treatment response. Unfortunately, the precise nature of this relationship is less than clear, as reflected by the fact that even now there are no established biomarkers that are used routinely in clinical practice to aid in diagnosis. This study also seeks to examine a comprehensive suite of biomarker measurements (MRI, neurophysiology, and genomics/proteomics) before and after rTMS treatment.
详细描述
rTMS is a Health-Canada- and FDA-approved treatment for treatment-resistant depression (TRD), using focused magnetic field pulses to stimulate brain regions involved in emotion regulation, safely and non-invasively. Though rTMS is often effective where medications or therapy fail, it requires a series of lengthy (~30-40 min) treatment sessions. A new form of rTMS called theta burst stimulation (TBS) has been shown to have greater effects on neural activity than conventional stimulation, despite requiring as little as 40 s of stimulation. The purpose of this study is to assess the efficacy and tolerability of an accelerated TBS protocol, administered 2 times a day in patients with TRD. In addition, the investigators aim to identify candidate biomarkers from a multimodal suite of neuroimaging, neurophysiologic and molecular measures that are predictors and correlates of response to rTMS treatment.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •are outpatients
- •are voluntary and competent to consent to treatment
- •have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent
- •are between the ages of 18 and 59
- •have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of > 3 in the current episode 105,106 OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants)
- •have a score > 18 on the HRSD-17 item
- •have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
- •able to adhere to the treatment schedule
- •Pass the TMS adult safety screening (TASS) questionnaire
- •have normal thyroid functioning based on pre-study blood work.
排除标准
- •have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months
- •have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
- •have active suicidal intent
- •are pregnant
- •have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms
- •have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
- •have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
- •have failed a course of ECT in the current episode or previous episode
- •have received rTMS for any previous indication due to the potential compromise of subject blinding
- •have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes
- •have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
- •if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
- •clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians
- •currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy
- •non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
研究组 & 干预措施
Single site rTMS
Each treatment session will consist of:
1200 pulses of iTBS over a posterior target location followed by a 60 minute interval, then 1200 pulses of iTBS over an anterior target location.
干预措施: rTMS (Device)
Dual site rTMS
Each treatment session will consist of:
600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location followed by a 60 minute interval, then 600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location.
干预措施: rTMS (Device)
结局指标
主要结局
17-item Hamilton Rating Scale for Depression (HRSD-17) Change
时间窗: 10 days
Change from baseline to 10 days
次要结局
- 17-item Hamilton Rating Scale for Depression (HRSD-17) Change(30 days)
研究者
Daniel Blumberger
Medical Head and Co-Director, Temerty Centre for Therapeutic Brain Intervention
Centre for Addiction and Mental Health