MOTOR-NF - a Randomized Controlled Trial of FMRI-based Neurofeedback for Motor Symptoms of Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- MDS-UPDRS (Unified Parkinson's Disease Rating Scale)
研究概览
简要总结
Rationale: Current treatment of patients with Parkinson's disease (PD) is mainly based on the modulation of neural activity in the motor circuits of the basal ganglia and cerebral cortex by either drug intervention (dopamine replacement therapy or dopaminergic medication) or deep brain stimulation (DBS). However, many Parkinson patients have an insufficient (long-term) response to medical treatments, and DBS is an invasive procedure with resource implications and potential side effects. Moreover, not all patients are eligible for DBS. Therefore, new ways of administering neuromodulation are needed. A potential avenue may be self-regulation of brain circuits through neurofeedback. Self-regulation of motor circuits through mental imagery and neurofeedback using real-time functional MRI (fMRI) signals has already been shown to be feasible, and there are also preliminary data on clinical benefits of such self-regulation training. We here aim to use the non-invasive fMRI-neurofeedback method to train patients in the regulation of brain circuits that are implicated in successful drug treatment and/or DBS.
Objective: To investigate brain mechanisms and efficacy of an fMRI-neurofeedback protocol that targets the brain's motor circuits through the basal ganglia.
Study design: Randomised controlled trial Study population: Patients with Parkinson's disease Investigation: In the experimental group, fMRI-neurofeedback will be administered in 4 separate sessions of about 2 hours each over approximately one month. The MRI measurement in each session will be approximately 60 minutes long and include upregulation training of brain activity in specific target areas by mental imagery. The fMRI signals are processed such that the patients get visual feedback about the success of the upregulation. In addition, patients are asked to practice the self-regulation strategies on a daily basis at home between the neurofeedback sessions. The control intervention will consist of mental imagery without neurofeedback.
Main study parameters/endpoints: Post-interventional improvement of motor symptoms of PD as assessed by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scale in the on-medication state.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This is a low-risk study where the main burden is participation time and MRI scans.
详细描述
Parkinson's disease (PD) is associated with progressive neurodegeneration of dopaminergic neurons of the substantia nigra. It is characterized by both motor and non-motor system manifestations. Dopamine replacement therapy or dopaminergic medication are the key therapeutic strategies, but deep brain stimulation (DBS) is increasingly being used in cases where drug response is/ has become insufficient or hampered by unacceptable side effects.
Neurofeedback (NF) entails training of self-regulation of brain regions or networks via mental imagery and real-time feedback of neural signals, for example obtained by functional MRI (fMRI). NF enables patients to develop personal strategies that are most effective in self-regulating brain areas and networks. Thereby, it can provide an individually tailored intervention. NF is a highly sustainable form of non-invasive neuromodulation because, once learnt, the self-regulation strategies can in principle be applied by patients whenever needed to overcome disease symptomology.
NF can be used to train patients to change their brain activity in different directions, or to modulate patterns of co-activation between regions. Mental imagery of moving one's own body (also called kinaesthetic imagery) can potentially be used to improve motor functions and neuroplasticity in PD. Kinaesthetic imagery is also a suitable strategy for increasing activation in the brain's motor network, and motor imagery training can be reinforced through combination with NF. A NF paradigm involving upregulation training of motor areas through kinaesthetic imagery thus has good plausibility for PD. The PI's group has shown proof-of-concept of such an fMRI-NF training (targeting the supplementary motor area, SMA) in PD and has recently completed a feasibility study of fMRI-NF targeting the putamen in 12 PD patients (NCT05627895). The aim of the current investigator-initiated study is to investigate the effects of putamen upregulation training on motor function and other outcome parameters in PD.
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 (Outcomes Assessor)
盲法说明
The outcome assessor will be unaware of which condition the participant is in.
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 Parkinson's disease.
- •Disease stage 1-3 according to the Hoehn and Yahr Scale
- •Age: 18 years or more
排除标准
- •Exclusion criteria for MRI (e.g., cardiac pacemaker, certain metallic implants)
- •History of psychotic disorder, bipolar disorder, or psychotic depression
- •Current use of illegal drugs (any in the last four weeks)
- •Current excessive alcohol consumption that interferes with daily functioning
- •A score on the Montreal Cognitive Assessment (MoCA) below 24/
- •Any disorder that would interfere with accurate and usable data acquisition.
结局指标
主要结局
MDS-UPDRS (Unified Parkinson's Disease Rating Scale)
时间窗: After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session)
Pre versus Post-interventional change in the MDS-UPDRS (Unified Parkinson's Disease Rating Scale) motor scale will be compared using t statistics. The MDS-UPDRS contains 65 scores, each with a range from 0 (no impairment) to 4 (severe impairment). The total scale ranges between 0 - 260, with 0 indicating no impairment and 260 indicating the highest level of impairment. As primary outcome measure we will use Part III: Motor Examination, which has 33 scores. The measurement at the last MRI session will be the primary endpoint.
次要结局
- Performance of Putamen neurofeedback training (fMRI analysis)(Measurements will be recorded at each MRI session (approx. 1 week intervals after screening and inclusion))
- Whole brain activation pattern changes (fMRI analysis)(Measurements will be recorded at each MRI session (approx. 1 week intervals after screening and inclusion))
- Neurofeedback training effects on non-motor symptoms(After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session))
- Correlation between NF success and distal finger tapping test (behavioral measure)(After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session))