Joan Ribas Araquistain Program for Research and Therapeutic Innovation in Prehabilitation, Rehabilitation and Comprehensive Approach to the Sequelae of Brain Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Feasibility_safety
研究概览
简要总结
The goal of the present pilot single-cohort feasibility trial is to investigate the feasibility and understand potential mechanisms of efficacy for Neuromodulation-Induced Cortical Prehabilitation (NICP) in adults with brain tumours and eligible for neurosurgery.
The main questions it aims to answer are:
- is the intervention feasible, in terms of adherence, retention, safety and patient's satisfaction;
- what are the mechanisms of neuroplasticity primed by NICP
Participants will undergo a prehabilitation protocol, consisting of daily sessions (total: 10-20 sessions) structured as follows:
- Intervention 1: non-invasive neuromodulation (TMS/tDCS).
- Intervention 2: motor and/or cognitive training, during or immediately after non-invasive neuromodulation, for about 60 minutes.
The timeline is structured as follows:
T1: baseline (before NICP) T2-T3: NICP period T4: after NICP T5: surgery T6: after surgery
Clinical, neuroimaging and neurophysiology assessments will be performed before NICP (T1), after NICP (T4), and after neurosurgery (T6). Feasibility outcomes will be determined during NICP protocol (T2-T3).
The objective of the proposed intervention is to progressively reduce the functional relevance of eloquent areas, which are healthy brain areas close with the tumour and thus exposed to the risk of being lesioned during surgery. In fact, previous studies have shown that temporary inhibition of eloquent areas (by neuromodulation) coupled with intensive motor/cognitive training promoted the activation of alternative brain resources, with a shift of functional activity from eloquent areas to areas functionally related, but anatomically distant from the tumour.
By moving the activation of key motor/cognitive functions away from the tumour, the risk of postoperative functional sequelae will be reduced; which in turn will falicitate a more radical tumour excision by the neurosurgeon.
详细描述
Neuromodulation-Induced Cortical Prehabilitation (NICP) is a relatively new approach in the neurosurgical field. It consists of priming neuroplastic changes before neurosurgery for brain tumours, in order to improve surgical outcomes and, hopefully, long-term survival and quality of life. The intervention comprises two elements:
- Neuromodulation (like transcranial magnetic stimulation, TMS, and transcranial direct current stimulation, tDCS). The goal of neuromodulation is to inhibit the eloquent areas, defined as brain areas functionally active and close to the tumour.
- Behavioural training (like motor training, cognitive training, or a combination). The function trained corresponds with the function of the eloquent area targeted by neuromodulation.
The two interventions are provided on a daily basis, and repeated over 10-20 consecutive weekdays. Notably, after the inhibition of the eloquent area there is a temporal window of about one hour, where intensive training of the same function requires the activation of alternative areas/pathways. By consolidating this alternative activation over multiple sessions, the outcome is a reduction in the functional relevance of eloquent areas, in favour of alternative resources anatomically distant from the tumour.
Only few case reports have been published so far, with very positive results obtained by means of invasive neuromodulation; the term 'invasive' means that a first neurosurgery was required to implant electrodes over eloquent areas for intracranial electrical stimulation, followed after few days/weeks by a second surgery for tumour removal. Despite relevant neuroplastic changes, the problem with this approach has been the high rate of adverse events occurred (infections, edema, pain, seizure) due to the invasiveness of the procedures. Therefore, by using a non-invasive neuromodulation approach, the goal of the present trial is to promote neuroplastic changes beneficial for neurosurgery, while at the same time ensuring no serious adverse events.
Further details on neuromodulation. Investigators will apply the most appropriate neuromodulation protocol, personalized based on whether to perform TMS and/or tDCS, individual resting motor threshold (for TMS), and target determination (related to eloquent areas).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of brain tumour requiring neurosurgery
- •ability to undertake at least 10 sessions of prehabilitation protocol
- •tumour location posing the patient at risk of developing post-operative neurological deficits, for instance at the level of upper limb motor function and speech production
- •ability to understand the general purpose of the prehabilitation program and understand simple instructions
- •being willing to participate and sign the informed consent
- •being able to sit unassisted for one hour.
排除标准
- •any contraindication for magnetic resonance imaging or transcranial magnetic stimulation
- •unstable medical conditions
- •musculoskeletal disorders that may significantly affect functional training
- •pain, depression, fatigue that may significantly affect functional training
- •history of alcohol/drug abuse
结局指标
主要结局
Feasibility_safety
时间窗: Throughout the intervention, which will last approximately 10 to 20 sessions (two to four weeks)
Adequate safety is defined by the absence of any serious adverse event
Feasibility_retention
时间窗: Throughout the intervention, which will last approximately 10 to 20 sessions (two to four weeks)
Sufficient retention is defined by at least 75% of enrolled patients completing the intervention
Feasibility_adherence
时间窗: Throughout the intervention, which will last approximately 10 to 20 sessions (two to four weeks)
Sufficient adherence is defined by attending at least 75% of the planned sessions
Feasibility_patient's satisfaction
时间窗: Throughout the intervention, which will last approximately 10 to 20 sessions (two to four weeks)
Self reported patient's satisfaction, as from the EORTC\* PATSAT C-33 questionnaire. All of the EORTC scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. in this case, higher score means higher patient's satisaction of the treatment received. \*European Organisation for Research and Treatment of Cancer (EORTC)
次要结局
- Clinical_upper limb_Deary-Liewald reaction time task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_lower limb and balance_Fugl Meyer Lower Extremity(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Neurological Assessment in Neuro-Oncology (NANO) scale(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_upper limb_9 Hole Peg Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_lower limb and balance_Brunel Balance Assessment(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Karnofsky Performance Status(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_upperl limb_Fugl-Meyer Upper Extremity(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_upper limb_Hand dynamometer(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Revised Barcelona Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Trail Making Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Wisconsin Card Sorting Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_resting state fMRI(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_fMRI_Finger tapping task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neurophysiology_TMS mapping_language function(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_lower limb and balance_Six minute walking test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_EORTC-QLQ-C30*(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_EORTC-FA12(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Rey Auditory Verbal Learning Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Symbol Digit Modalities Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Hayling Test(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_EORTC-BN20(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_WMS-IV Wechsler Memory Scale(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_fMRI_Comprehensive auditive task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neurophysiology_TMS mapping_hotspot(Baseline (before the intervention protocol))
- Clinical_WAIS-III Wechsler Adult Intelligence Scale(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Continuous Performance Test-III(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_PMR Verbal fluency by letters.(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_fMRI_Semantic decision task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neurophysiology_TMS mapping_resting motor threshold(Baseline (before the intervention protocol))
- Surgical outcomes(Within the first week after surgery)
- Neuroimaging_fMRI_Ankle flexion task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Clinical_Hospital Anxiety and Depression Scale(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_structural MRI(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_fMRI_Word generation task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neuroimaging_fMRI_Tongue movement task(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))
- Neurophysiology_TMS mapping_motor function(At baseline (before the intervention), at the end of the intervention (but before neurosurgery), and at the first available follow up (from one month up to one year after surgery))