Clinical, Molecular and Electrophysiological Profiling of Parkinson's Disease: the Role of Non-pharmacological Therapies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- MOLECULAR PROFILING OF PD PATIENTS (n=400)
研究概览
简要总结
In Parkinson's disease (PD), direct evidence linking inflammation to the harmful activities of alpha-synuclein (a-syn) aggregates, the disease onset, and its progression is still lacking. This translational project aims to reveal the causal relationship between a-syn and inflammation. The investigators will also investigate the mechanisms underlying the beneficial effects of two non-pharmacological approaches, motor exercise and neuromodulation, with particular focus on neuroinflammation and brain-derived neurotrophic factor (BDNF) production. the investigators will investigate the molecular pathways and synaptic alterations underlying disease progression. This will be paralleled by a clinical study, in which clinical assessment will be associated with cerebrospinal fluid (CSF) and blood neurodegeneration and inflammatory biomarkers measures. Then, the investigators will test the hypothesis that intensive exercise and neuromodulation may reduce neuroinflammation and a-syn spreading via the activation of BDNF-related pathways.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •clinically established diagnosis of PD according to the Movement Disorders Society (MDS) diagnostic criteria
- •Hoehn & Yahr (H&Y) stage between 1 and 3
排除标准
- •Pregnancy
- •Oncological or autoimmune comorbidities
研究组 & 干预措施
physical activity
干预措施: physical activity (Other)
sedentary
iTBS active
干预措施: iTBS (Other)
iTBS sham
干预措施: iTBS (Other)
Biomarkers
结局指标
主要结局
MOLECULAR PROFILING OF PD PATIENTS (n=400)
时间窗: at enrolling
Biomarkers related to axonal damage (total tau (t-Tau), neurofilament light chain, (NfL), and phosphorylated neurofilament heavy chain, (p-NfH), synaptic dysfunction (a-synuclein (a-syn) and neurogranin, (Ng)), neuroinflammation (soluble triggering receptor expressed on myeloid cells 2, sTREM2, and chitinase-3- like protein 1, YKL-40) will be analysed in cerebrospinal fluid (CSF) and blood samples and extracellular vesicles (EVs) (UO1, UO2) (for all the biomarkers, ng/ml).
ELECTROPHYSIOLOGICAL PROFILING OF PD PATIENTS (n=400)
时间窗: at enrolling
Motor evoked potentials (MEPs) from the First Digital Interosseus muscle of the most affected hand of each patient, a brief pattern of iTBS will be applied to promote enhancement of cortical excitability. MEPs size will be then assessed again using single-pulse TMS.
CLINICAL PROFILING OF PD PATIENTS (n=400)
时间窗: at enrolling
patients will be evaluated by means of validated clinical scales Movement disorders society-unified Parkinson's Disease Rating Scale (min 0- max 260, better clinical conditions has lower scores)
次要结局
- NMSS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- UPDRS CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240) CLINICAL PROFILING OF PD PATIENTS (n=400)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- MOLECULAR CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)
- ELECTROPHYSIOLOGICAL CHANGES AFTER NON-PHARMACOLOGICAL INTERVENTIONS (n=240)(at the end of the non-pharmacological intervention (2 weeks for TMS branches, 3 months for physical activity branches) and 3 and 6 months after)