Building on Previous Evidence: A Mechanistic Clinical Trial of Personalized rTMS for Chronic Pain
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Pain intensity (Visual analogue scale)
研究概览
简要总结
Previous research has demonstrated that repetitive magnetic brain stimulation can be an effective adjunctive treatment for several conditions, including chronic pain. However, current stimulation protocols are typically standardized and do not account for individual variability in brain function. This uniform, one-size-fits-all approach results in only about 40% of patients experiencing meaningful clinical benefit, while the remainder show little to no improvement. To address this limitation, the present study will investigate how magnetic stimulation can be tailored to individuals with chronic pain. By analyzing each participant's brain signals prior to treatment, we aim to personalize stimulation parameters to better match individual neural characteristics and potentially enhance therapeutic outcomes. The design of this study builds directly on the findings of a previous clinical trial.
详细描述
This study builds directly on previous clinical findings identifying four cortical targets-primary motor cortex (M1), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and the posterior insula (PSI)-as exhibiting neurophysiological properties potentially useful for guiding individualized repetitive transcranial magnetic stimulation (rTMS) target selection. Earlier results demonstrated that chronic pain patients with low alpha-band intertrial coherence (ITC) over M1 were more likely to respond to stimulation of M1, whereas patients with high alpha-band ITC showed a greater likelihood of responding to stimulation of PSI, ACC or DLPFC. These findings suggest that specific electroencephalography (EEG) connectivity markers may help predict the cortical target most likely to provide therapeutic benefit for an individual patient.
Building on this evidence, the present trial will classify participants according to their pre-treatment transcranial magnetic stimulation-electroencephalography (TMS-EEG) connectivity profiles and assign treatment to the cortical region with the highest predicted probability of clinical response.
A total of 90 patients with chronic pain will be enrolled in a double-blind, randomized, two-parallel-arm clinical trial comparing the analgesic effects of individualized target selection with those of the standard rTMS protocol. Participants will be randomized 1:1 to:
- Individualized targeting, in which the rTMS site is selected based on each participant's TMS-EEG connectivity profile
- Standard stimulation, representing the conventional rTMS approach for pain relief.
At baseline, participants will complete standardized questionnaires and undergo neurophysiological assessments, including single-pulse TMS-EEG for target classification. The induction phase will then begin, consisting of five consecutive daily rTMS sessions delivered Monday through Friday. Each session lasts 30 minutes, including 15 minutes of active stimulation.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of chronic pain (present most of the days for more than 3 months).
- •Pain with a mean pain intensity between 3-9 on a 0-10 pain scale (where 0 means no pain and 10 means the worst pain imaginable).
- •Speak and understand English or Danish
排除标准
- •Pregnant or breastfeeding
- •Current uncontrolled major depression as the main diagnosis
- •Current history of substance abuse
- •Lack of ability to cooperate, to fully understand the protocol or any difficulty in filling out questionnaires (e.g., due to language or cognitive problems)
- •Formal contraindications to TMS application (presence of epilepsy, cranial implanted ferromagnetic devices, e.g., intracranial neurostimulator or cochlear implants, tattoos with metal ink on the face or permanent make up with metal in the face )
- •Unable to answer the "Transcranial Magnetic Stimulation Adult Safety Screen" screening questionnaire.
- •Participation in other research protocols within 1 month before the inclusion.
研究组 & 干预措施
Active Comparator : Classical rTMS
The patients will receive repetitive transcranial magnetic stimulation according to the classical treatment
干预措施: Classical repetitive trancranial magnetic stimulation to M1 (Device)
Experimental: Personalized Target Arm
The patients will receive repetitive transcranial magnetic stimulation (rTMS) to target showing the optimal connectivity during the TMS-EEG assessment one week before starting the treatment
干预措施: Personalized Target Arm (Device)
结局指标
主要结局
Pain intensity (Visual analogue scale)
时间窗: Visual analogue scale will be assessed before treatment, after 2 months, and again after 3 months. Responders are those with ≥30% pain reduction at the end of maintenance compared to average pain intensity the week before baseline assessment.
The '0' represents 'no pain' at all, and '100' represents the 'worst possible pain' that the individual can imagine.
次要结局
- Connectivity analysis(Connectivity changes will be investigated before the treatment and immediately after 2 months of treatment.)
- Quality of life (EQ-5D)(Quality of life changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.)
- Patients' Global Impression of Change(Patients' Global Impression of Change will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment)
- Short Brief Pain Inventory(Short Brief Pain Inventory changes will be investigated before the treatment, immediately after 2 months of treatment, and again after 3 months of treatment.)
- Connectivity analysis(Connectivity changes will be investigated before the treatment and immediately after 2 months of treatment.)
研究者
Enrico De Martino
Principal investigator
Aalborg University