Clinical trial NCT05799690: Comparison of Different Rehabilitation Protocols in Parkinson's Disease With Postural Instability and Gait Disorders
Official title: Multiparametric Biomarkers to Predict the Response to Different Protocols of Motor-cognitive Rehabilitation in Parkinson's Disease Subjects With Postural Instability and Gait Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Gait
Rehabilitation
Biomarkers
Magnetic resonance imaging
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera Universitaria Integrata Verona
First posted: 2023-04-05
Enrollment: 80
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-blind randomized controlled trial. Fifty PD patients are randomly divided into two groups: 25 in DUAL-TASK+AOT-MI (experimental) and 25 in the DUAL-TASK (active comparator). Half of the patients are further randomized to repeat the treatment (DUAL-TASK+AOT-MI_DOUBLE and DUAL-TASK_DOUBLE). The assessors are blinded to the group allocation. In addition, a group of 20 healthy age- and sex-matched control is included at baseline
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: Inclusion criteria 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

Exclusion criteria:

* 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.

Primary outcomes:
measure: Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
Secondary outcomes:
measure: Total execution time of Timed Up and Go test (TUG)
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Total execution time of Timed Up and Go test with manual dual-task (TUG-MAN)
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Brain functional changes during functional magnetic resonance imaging (MRI) tasks
timeFrame: Baseline, week 6 and week 28
measure: Serum concentration of Neurofilament light chain (NfL)
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of Glial Fibrillary Acid Protein (GFAP)
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of Phosphorylated Tau (P-Tau)
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of Tau
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of B42
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of B40
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of Alpha-synuclein
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Serum concentration of Brain Derived Neurotrophic Factor (BDNF)
timeFrame: Baseline, week 6, week 14 and week 28.
measure: Activity Balance Confidence questionnaire (ABC) score
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: 10-meter walk test (10MWT) time
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Mini Balance Evaluation System Test (MiniBESTest) score
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Five-time sit-to-stand (5STS) time
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Parkinson's Disease Questionnaire (PDQ-39) score
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Stride length
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Gait velocity
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients
measure: Kinesthetic and Visual Imagery Questionnaire (KVIQ)
timeFrame: Baseline, week 6 and week 28.
measure: New Freezing of Gait Questionnaire (NFoG-Q)
timeFrame: Baseline, week 6, week 14 and week 28. At week 20 only for patients
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele
city: Verona
country: Italy
facility: Neurology Unit, Azienda Ospedaliera Universitaria Integrata di Verona
Study officials:
References: