Multiparametric Biomarkers to Predict the Response to Different Protocols of Motor-cognitive Rehabilitation in Parkinson's Disease Subjects With Postural Instability and Gait Disorders
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)
研究概览
简要总结
The aim of the study is to compare the effects of 2 different dosages and modalities of motor-cognitive rehabilitation in Parkinson's disease with postural instability and gait disorders (PD-PIGD) on clinical features, neuroimaging and blood-based biomarkers at short-term (2 months) and long-term (7 months) follow-up. Fifty subjects with PD-PIGD will be randomized in 2 training groups: DUAL-TASK+AOT-MI and the DUAL-TASK groups. The DUAL-TASK+AOT-MI group will perform a dual-task gait/balance training consisting of action observation training (AOT) and motor imagery (MI) combined with practicing the observed-imagined exercises; DUAL-TASK group will perform the same exercises combined with watching landscape videos. The training will last 6 weeks, 3 times/week, 1 hour per session.
Before and after training (W6), all the patients will undergo neurological, gait/balance, cognitive/behavioral, magnetic resonance imaging (MRI) and serum biomarkers evaluations. Neurological, gait/balance, cognitive/behavioral assessments and serum biomarkers will be also repeated at the 14-week follow-up (W14) to assess maintenance of results.
Patients of both DUAL-TASK+AOT-MI and DUAL-TASK groups will be further randomized to repeat the training (6 weeks, 3 times/week, 1 hour each session) starting at W14 (DUAL-TASK+AOT-MI_DOUBLE and DUAL-TASK_DOUBLE groups). After six weeks (W20) all the subjects repeating the training will be evaluated (neurological, gait/balance, cognitive/behavioral assessments). At 28-week follow-up (W28), the whole sample of patients will be assessed with neurological, gait/balance, cognitive/behavioral, MRI and serum biomarkers evaluations. All MRI scans will be acquired at least 12 hours after last dopaminergic therapy administration to mitigate the pharmacological effects on neural activity. Twenty age- and sex-matched healthy controls will be recruited to perform gait/balance and cognitive/behavioral assessments, blood sample and brain MRI acquisition at baseline. The secondary aims of the study are to define the neuroimaging and blood-based biomarkers of PD-PIGD patients presenting different clinical features (e.g. presence of mild cognitive impairment, freezing of gait, falls and mood disturbances) and to evaluate the role of blood-based and neuroimaging biomarkers, together with clinical characteristics, in predicting the response to different dosages of rehabilitation in PD-PIGD throughout the development of a machine-learning algorithm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
Physiotherapist, neurologists, neuropsychologists and radiologist assessing the patients are blinded to group allocation.
入排标准
- 年龄范围
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for PD patients:
- •45 years ≤ age ≤ 85 years;
- •Idiopathic PD according to the Movement Disorders Society (MDS) diagnostic criteria
- •Hoehn & Yahr (H&Y) score <= 4
- •PIGD phenotype
- •Stable dopaminergic medication for at least 4 weeks and without any changes during the observation period (28 weeks)
- •No dementia according to Litvan's criteria and Mini-Mental Status Examination score (MMSE) >= 24
- •No significant tremor/involuntary movements that could determine artifacts during the MRI acquisition
- •Oral and written informed consent to study participation
- •Inclusion criteria for healthy controls:
- •sex-matched and age-matched (age range: mean age of PD years ± 15 years);
- •oral and written informed consent to study participation
排除标准
- •Medical conditions or substance abuse that could interfere with cognition;
- •Any major systemic, psychiatric, neurological, visual, and musculoskeletal disturbances or other causes of walking inability;
- •Contraindications to undergoing MRI examination;
- •Brain damage at routine MRI, including lacunae and extensive cerebrovascular disorders;
- •Denied oral and written informed consent to study participation.
研究组 & 干预措施
DUAL-TASK+AOT-MI
Dual-task gait and balance training with cognitive facilitations (action observation and motor imagery) for six weeks.
干预措施: Gait and balance training with dual-task + action observation and motor imagery (six weeks) (Behavioral)
DUAL-TASK
Dual-task gait and balance training with vision of landscape videos for six weeks.
干预措施: Gait and balance training with dual-task (six weeks) (Behavioral)
DUAL-TASK+AOT-MI_DOUBLE
Dual-task gait and balance training with cognitive facilitations (action observation and motor imagery) repeated two times (twelve weeks: 6 + 6).
干预措施: Gait and balance training with dual-task + action observation and motor imagery (twelve weeks: 6 + 6) (Behavioral)
DUAL-TASK_DOUBLE
Dual-task gait and balance training with vision of landscape videos repeated two times (twelve weeks: 6 + 6).
干预措施: Gait and balance training with dual-task (twelve weeks: 6 +6) (Behavioral)
Healthy subjects
Age- and sex-matched healthy subjects recruited to compare gait, neuropsychological, serum and functional magnetic resonance imaging characteristics at baseline.
结局指标
主要结局
Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)
时间窗: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
Changes in time taken to complete the timed up and go test with cognitive dual-task: patients are asked to stand up from a chair, walk for three meters, turn and walk back to the chair while counting backwards by 3 starting from 100. Assessment during ON medication phase.
次要结局
- Serum concentration of Neurofilament light chain (NfL)(Baseline, week 6, week 14 and week 28.)
- Serum concentration of Phosphorylated Tau (P-Tau)(Baseline, week 6, week 14 and week 28.)
- Serum concentration of B40(Baseline, week 6, week 14 and week 28.)
- Serum concentration of Tau(Baseline, week 6, week 14 and week 28.)
- Total execution time of Timed Up and Go test with manual dual-task (TUG-MAN)(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Brain functional changes during functional magnetic resonance imaging (MRI) tasks(Baseline, week 6 and week 28)
- Serum concentration of Glial Fibrillary Acid Protein (GFAP)(Baseline, week 6, week 14 and week 28.)
- Total execution time of Timed Up and Go test (TUG)(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- 10-meter walk test (10MWT) time(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Cambridge Neuropsychological Test Automated Battery (CANTAB)(Baseline, week 6, week 14 and week 28. At week 20 only for patients)
- Serum concentration of B42(Baseline, week 6, week 14 and week 28.)
- Activity Balance Confidence questionnaire (ABC) score(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Serum concentration of Alpha-synuclein(Baseline, week 6, week 14 and week 28.)
- Serum concentration of Brain Derived Neurotrophic Factor (BDNF)(Baseline, week 6, week 14 and week 28.)
- Mini Balance Evaluation System Test (MiniBESTest) score(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Parkinson's Disease Questionnaire (PDQ-39) score(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Stride length(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Gait velocity(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- New Freezing of Gait Questionnaire (NFoG-Q)(Baseline, week 6, week 14 and week 28. At week 20 only for patients)
- Five-time sit-to-stand (5STS) time(Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.)
- Kinesthetic and Visual Imagery Questionnaire (KVIQ)(Baseline, week 6 and week 28.)
研究者
Prof. Massimo Filippi
Prof
IRCCS San Raffaele