Effects of Intensive Multidisciplinary Rehabilitation and Identification of New Biomarkers in Response to an Integrated Motor-Cognitive and Aerobic Exercises Approaches in People With Parkinson's Disease
试验速览
- 阶段
- 不适用
- 入组人数
- 72
- 试验地点
- 2
- 主要终点
- Serum biomarkers in neuron derived extracellular vesicles (NDEVs)
研究概览
简要总结
Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms such as rigidity, bradykinesia, resting tremor, cognitive and autonomic dysfunctions, gait and balance difficulties.
The impairment of gait, balance and cognitive performances is partially responsive to dopaminergic medications. This emphasizes the importance of non-pharmacological interventions for people with PD (pwPD).
Intensive multidisciplinary motor and cognitive rehabilitation has been proposed as a complementary and effective treatment for managing pwPD.
Several structural and physiological mechanisms have been suggested to underpin exercise-induced neuroplastic changes in PD, such as enhanced synaptic strength and preservation of dopamine neurons. To date, studies on brain changes induced by motor and cognitive exercises in pwPD have been small-scaled and uncontrolled.
Identifying accessible and measurable biomarkers for monitoring the events induced by intensive motor and cognitive rehabilitation program would help in testing the treatment effectiveness and would allow personalization of rehabilitation strategies by predicting patients' responsiveness.
Based on validated clinical assessments of intensive multidisciplinary rehabilitation treatment, the project will test the ability of a new set of biomarkers to evaluate rehabilitative outcomes in a cohort of people with PD.
详细描述
While pharmacological treatment is helpful in the early stages of the disease, increased attention has been given to rehabilitation that may lead to clinical improvements in motor and non-motor impairments.
Recently synthesized evidence suggests that physical exercise may lead to neuroplastic changes at the functional, structural and molecular levels.
Accessible and measurable biomarkers are needed to monitor the disease progression and the neurobiological changes resulting from pharmacological and rehabilitative treatments, also can be a useful and valuable tool to test rehabilitation effectiveness.
The present project will start from the reliable clinical assessment of rehabilitation effectiveness of an intensive multidisciplinary rehabilitation program, to verify the ability of a new panel of measurable biomarkers to assess neurobiological and functional changes in pwPD.
The purpose of this study is to determine the effects of an intensive multidisciplinary, aerobic, motor-cognitive rehabilitation treatment on accessible and measurable molecular biomarkers (primary outcome); balance and gait performance; aerobic capacity; motor and non-motor symptoms; cognitive functions; neuroimaging biomarker (secondary outcomes) in comparison to an active control group receiving a home-based self-treatment program. Thereafter, the investigators aim to relate the effects seen in motor and "non-motor" behavior to changes in biomolecular and neuroimaging markers.
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PD diagnosis according to MDS Criteria (MDS clinical diagnostic criteria for Parkinson's disease, Postuma et al., 2015);
- •Modified Hoehn&Yahr (H&Y): stages from 1.5 to- 3;
- •Stable pharmacological treatment in the last 4 weeks.
排除标准
- •Vascular, familiar and drug- induced forms of parkinsonism, other known or suspected causes of parkinsonism (metabolic, brain tumor etc) or any suggestive features of atypical parkinsonism;
- •Significant comorbidities and/or severe systemic diseases that would preclude exercise participation (eg.recent surgery, unstable cardiac dysfunction, anemia, hepatosis, pulmonary disorders, chronic renal failure; auditory, visual and/or vestibular dysfunctions, presence of DBS); previously diagnosed psychiatric diseases.
- •Dementia as defined by Montreal Cognitive Assessment (MoCA Test) Correct Score<15.51 (Santangelo et al., 2014);
- •Rehabilitation treatment in the previous 4 weeks.
结局指标
主要结局
Serum biomarkers in neuron derived extracellular vesicles (NDEVs)
时间窗: 18 weeks
Oligomeric α-synuclein (α-syn) ng/ml; SNARE complex: Syntaxyn-1(STX-1A) (ng/ml), VAMP-2 (ng/ml) and SNAP-25 (ng/ml); Brain-Derived Neurotrophic Factor (BDNF) (ng/ml), pro-BDNF (ng/ml), Glial cell line-derived Neurotrophic factor (GDNF) (ng/ml) Cerebral dopamine neurotrophic factor (CDNF) (ng/ml)
Blood Biomarkers
时间窗: 18 weeks
Pro- \[IL-1β (pg/ml), Tumour Necrosis Factor alpha (TNFα) (pg/ml), Interferon gamma (IFN-γ) (pg/ml), IL-6 (pg/ml), IL-18 (pg/ml)\], Anti-inflammatory (IL-10) (pg/ml) cytokines.
次要结局
- IdeoMotor praxis(18 weeks)
- Balance(18 weeks)
- Aerobic capacity and endurance(18 weeks)
- Strenght(18 weeks)
- Non-Motor symptoms(18 weeks)
- Extradimensional non-verbal set-shifting(18 weeks)
- Depression(18 weeks)
- Dynamic Balance(18 weeks)
- Gait speed(18 weeks)
- Sleep quality(18 weeks)
- Frontal lobe functioning(18 weeks)
- Fatigue(18 weeks)
- Motor and non-motor symptoms(18 weeks)
- Daytime sleepiness(18 weeks)
- Parkinson's disease-specific health related quality of life(18 weeks)
- Verbal short-term and working memory(18 weeks)
- Cognitive interference inhibition(18 weeks)
- Apathy(18 weeks)
- Impulsivity(18 weeks)
- Daily self-care activities(18 weeks)
- Cerebral blood flow(18 weeks)
- Gait Analysis(18 weeks)
- Rapid eye movement sleep behavior disorder(18 weeks)
- Pain Intensity(18 weeks)
- Global Cognitive Functioning(18 weeks)
- Visuo-spatial memory(18 weeks)
- Language production and non-motor processing speed(18 weeks)
- Anxiety(18 weeks)
- Impulsive Control Disorders(18 weeks)
- Autonomic Symptoms(18 weeks)
- Verbal episodic memory(18 weeks)
- Visuo-constructional ability(18 weeks)
- Non-verbal reasoning(18 weeks)
- Extradimensional verbal set-shifting(18 weeks)
- Speed information processing(18 weeks)
- Anhedonia(18 weeks)
- Alexithymia(18 weeks)
- Functional disability(18 weeks)
- Home-based motor activity monitoring(18 weeks)
- Behavioral disturbances(18 weeks)
- Caregiver burden(18 weeks)
- Brain functional connectivity(18 weeks)