Real-World NeuroModulate: Investigating Non-Invasive Brain Stimulation for Neuropsychiatric Disorders at TUM
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Difference in imaging parameter trajectory between Responders and Non-Responders across multi-modal Tissue Parameter Maps.
研究概览
简要总结
In this study, patients diagnosed with a depressive syndrome and with a clinical indication for treatment will receive an acute course of transcranial magnetic stimulation (TMS). The treatment consists of 20 TMS sessions administered over a period of four weeks (five sessions per week).
Magnetic resonance imaging (MRI) will be performed at four time points: prior to the start of treatment, after 10 treatment sessions, after completion of all 20 sessions, and at a three-month follow-up after the end of treatment. The MRI data will include different imaging modalities to assess treatment-related neurobiological changes.
The primary objective is to investigate changes in neuroimaging markers over the course of TMS treatment and to examine their associations with clinical response and behavioral as well as clinical outcome measures. Another key goal of the study is the identification of markers allowing for early prediction of treatment response to TMS and, additionally, for the prediction of relapse at follow-up.
详细描述
This study investigates the neurobiological effects of standard intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC) in patients with a depressive syndrome undergoing routine clinical TMS treatment. The study follows a prospective, naturalistic longitudinal design and focuses on the association between iTBS-induced clinical change and repeated multimodal magnetic resonance imaging (MRI) measurements. The primary scientific objective is the identification of imaging-correlates of treatment response, as well as the identification of biomarkers that allow for early prediction of treatment response and later relapse following iTBS.
Patients who receive a clinical indication for TMS as part of routine psychiatric care undergo an acute treatment course consisting of 20 iTBS sessions administered over four consecutive weeks with five sessions per week. The treatment protocol is fixed to standard intermittent theta burst stimulation applied over the left DLPFC. The clinical decision to initiate TMS is made independently of study participation.
The severity of depressive symptoms is assessed at baseline (prior to the first session), as well as after two weeks and after four weeks of treatment, using both self-report and clinician-rated scales (HDRS and MADRS, as well as the BDI). Response is defined as at least a 50% reduction in symptoms, operationalized as a minimum 50% decrease in the respective scale scores. The MADRS is used to classify participants as responders versus non-responders. In addition, sociodemographic data, personality characteristics (degree of sensation-seeking personality), and history of traumatization (CTQ) are collected at baseline.
Prior to treatment initiation, the individual resting motor threshold (rMT) is determined by stimulation of the primary motor cortex, using either visual detection of motor evoked responses or surface electromyography. The stimulation intensity for iTBS is set at 120 % of the individual rMT. In cases where this intensity is not tolerated, e. g. due to pain, the intensity will be reduced to 80% of the individual rMT.
The iTBS protocol consists of bursts of three pulses at 50 Hz repeated at intervals of 200 ms (5 Hz). Each train lasts 2 seconds and is followed by an 8-second inter-train interval. One iTBS session has a total duration of 3 minutes and 9 seconds and comprises 600 pulses. One single iTBS session is delivered per treatment day throughout the four-week acute stimulation phase. No accelerated, high-intensity, or multi-session-per-day protocols are applied.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18 years or older
- •Clinical indication for non-invasive brain stimulation due to a depressive episode (e.g., unipolar or bipolar depression) or predominant depression-associated symptoms (e.g., negative symptoms in schizophrenia-spectrum disorders)
- •Insufficient response to first-line treatments and/or patient preference for brain stimulation treatment
- •Capacity and willingness to provide written informed consent
排除标准
- •Acute suicidal risk
- •Presence of a significant neurological disorder or condition, including:
- •Increased intracranial pressure
- •Space-occupying brain lesions
- •History of cerebrovascular accident within the last 12 months
- •Incidental structural brain abnormalities on MRI requiring further diagnostic clarification
- •For TMS specifically:
- •Non-removable ferromagnetic implants in or near the stimulation site (e.g., cochlear implants, implanted neurostimulators, metallic clips or nails)
- •Other treatment-relevant ferromagnetic implants (e.g., cardiac pacemakers)
研究组 & 干预措施
Patients with depressive Syndrom receiving regular iTBS treatment
Patients with depressive Syndrom receiving regular iTBS treatment over 4 weeks, no relevant personality disorder
干预措施: iTBS Treatment (Other)
结局指标
主要结局
Difference in imaging parameter trajectory between Responders and Non-Responders across multi-modal Tissue Parameter Maps.
时间窗: From enrollment to the end of treatment (4 weeks).
We aim to identify an imaging-based correlate for treatment response. Therefore, we will compare the dynamic of tissue parameter maps (TPMs) between Responders and Non-Responders. We will realize this by employing a voxel-wise, flexible factorial statistical framework with two main independent variables, TIME and RESPONDER. TIME will reflect the timepoint of the scan (before treatment, during treatment, after treatment). RESPONDER will denote whether a participant is a reponder or not. The responder status will be defined via the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) before and after treatment (cutoff at least 50% MADRS reduction). The main outcome will be generated by testing for the interaction effect of TIME and RESPONDER. This will test for voxel values in which the longitudinal change is different between responders and non-responders. This statistical framework will be the main framework for all modalities with voxel-based outcomes.
次要结局
- Difference in connectome trajectory between Responders and Non-Responders across multi-modal connectomes.(From enrollment to the end of treatment (4 weeks).)
- Prediction of Responder Status using Structural and Functional Networks at Baseline(Data generated at enrollment.)
- Prediction of Responder Status using Structural and Functional Networks at Baseline and Mid-Therapy(Enrollment to two weeks after therapy start.)
- Prediction of Responder Status using Tissue Parameter Maps at Baseline(Data generated at enrollment.)
- Prediction of Responder Status using Tissue Parameter Maps at Baseline and Mid-Therapy(Enrollment to two weeks after therapy start.)