Treatment of Major Depression by Magnetic Stimulation Repeated Transcranial on Prefrontal Cortex: Study of Underlying Mechanisms
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change from baseline connectivity with theta wave on EEG at D5 (immediate effect) :
研究概览
简要总结
The study aims to evaluate the impact of repeated Transcranial Magnetic Stimulation (rTMS) on underlying neuronal mechanisms of adults suffering from major depression disorder (MDD). Short- and long-term effects are assessed by High-Resolution electroencephalography (HR-EEG) or Magnetic Resonance Imaging (MRI) records, experimental tasks and self-rated scales.
详细描述
Depression is associated with functional and structural changes in the brain, notably in DLPFC (DorsoLateral PreFrontal Cortex). High-frequency rTMS (10 Hz) applied to the left DLPFC is associated with a response rate 3.75 times and remission 2.52 higher than placebo for the treatment of MDD with more reproducible results than those observed for the others rTMS stimulation modalities (low frequency, iTBS5). rTMS is validated as an indication for the treatment of MDD by all learned societies and regulatory authorities in a large number of countries, except in France. Limiting factors concern the lack of knowledge of the action mechanisms, due in particular to the absence of studies based on animal models, the focused application of TMS in rodents being a challenge that few teams have mastered. The rationale for the therapeutic use in the treatment of MDD is now based on some functional brain imaging data showing that rTMS induces a lasting change in brain activity at the site of stimulation (CPFDL) but also in remote interconnected areas such as the limbic region or the amygdala. The DEPSTIM clinical project is part of a translational project with a fundamental approach in rodents.
The main objective is to demonstrate that remission following rTMS of CPFDL occurs via the activation of CPFDL projections to these dysfunctional subcortical areas in MDD.
With a prospective, open design, this study aims to evaluate the impact of iTBS over the left DLPFC on neuronal mechanisms of adults suffering from MDD. Subjects will be submitted to 25 intermittent TBS (iTBS) stimulation sessions for five consecutive days (5 sessions of 9.5 minutes/day, 1,800 pulses per session, 90% of resting motor threshold, placed over the left DLPFC, as mentionned by Cole et al, 2018 (Stanford Neuromodulation Therapy: SNT)). Baseline measures will be compared to those obtained immediately after the end of sessions (Day 5 (D5): short-term effects with HR-EEG analysis), and 30 days (D30) later (long-term effects with MRI analysis).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MDD (Diagnostic and Statistical Manual of Mental Disorders V [DSM-V] and (Mini International Neuropsychiatric Interview [MINI] criteria, QIDS-C16≥18)
- •Right-handed
- •No response at a first antidepressant
- •Under AD ≥ 6 weeks
- •No contraindications for rTMS and MRI
- •Absence of addictive comorbidities
- •Absence of severe progressive neurologic and/or somatic pathologies (specially tumors, neurodegenerative diseases)
- •Inpatients or outpatients of Adult Psychiatric Department
- •Signed informed consent form
- •Subjects affiliated to or beneficiary from a French social security regime
排除标准
- •Subjects under 35 years old or over 65 years old
- •Treated with over 4 AD for the current episode
- •ECT or rTMS for current episode
- •BZD or antiepileptic (except pregabalin up to 75 mg / d, zopiclone ≤7.5 mg / d)
- •Left-handed
- •Subject under measure of protection or guardianship of justice
- •Presence of psychiatric comorbidities
- •Subject beneficiary from a legal protection regime
- •Subject unlikely to cooperate or low cooperation stated by investigator
- •Subject not covered by social security
- •Pregnant woman
- •Subject being in the exclusion period of another study or provided for by the "National Volunteer File
结局指标
主要结局
Change from baseline connectivity with theta wave on EEG at D5 (immediate effect) :
时间窗: baseline (Day 0), Day 5 post-treatment
changes in brain connectivity will be analyzed with theta wave
Change from baseline connectivity with beta wave in EEG at D5 (immediate effect)
时间窗: baseline (Day 0), Day 5 post-treatment
changes in brain connectivity will be analyzed with beta wave
Change from baseline connectivity with P3 wave EEG at D5 (immediate effect)
时间窗: baseline (Day 0), Day 5 post-treatment
changes in brain connectivity will be analyzed with P3 wave
Change from baseline connectivity with fMRI at D30 (prolonged effect) : Resting State Magnetic Resonance Imaging (MRI)
时间窗: baseline (Day 0), Day 30 post-treatment
Resting State MRI will allow us to investigate the functional connectivity in the brain, by looking at resting state networks
次要结局
- Severity of depressive symptoms evaluated by the patient(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- Impulsivity(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- Average adjusted pump scores on the Balloon Analogue Risk Task (BART)(baseline (Day 0), Day 12 post-iTBS)
- To assess the optimal b-value (a key parameter) for DTI (Diffusion Tensor Imaging)(baseline (Day 0), Day 30 post-iTBS)
- Smoking (tobacco addiction) according to the Fagerström test(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- Delay Discounting(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- C-Reactive Protein (CRP) concentrations(baseline (Day 0), Day 12 post-iTBS)
- Severity of depressive symptoms evaluated by the clinician(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- Cognitive assessment(baseline (Day 0), Day 30 post-iTBS)
- Dimensions of personality(baseline (Day 0), Day 5 (end of iTBS sessions), Day 12 and Day 30 post-iTBS)
- Motivation(baseline (Day 0), Day 12 post-iTBS)
- Social exclusion(baseline (Day 0), Day 12 post-iTBS)
- Serum Interleukin-6 (IL-6) level(baseline (Day 0), Day 12 post-iTBS)