Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson's Disease
- Conditions
- Parkinsonian DisordersBiomarkersNeurodegenerative DiseasesPhysiotherapyRehabilitation OutcomeMovement DisordersSynucleinopathiesParkinson DiseaseBasal Ganglia DiseasesCentral Nervous System Diseases
- Interventions
- Behavioral: Multidisciplinary Intensive RehabilitationBehavioral: Muscle-stretching and active mobilization exercises
- Registration Number
- NCT05452655
- Lead Sponsor
- Fondazione Don Carlo Gnocchi Onlus
- Brief Summary
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.
- Detailed Description
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.
To achieve this purpose, the study is designed as a Randomized Controlled Trial (RCT) and participants will be recruited at Fondazione Don C. Gnocchi-ONLUS, IRCCS S. Maria Nascente. Seventy-two subjects with a diagnosis of PD in accordance of MDS criteria will be randomly allocated to the experimental (EXP) or control group (CTR).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 72
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intensive Outpatient Integrated Motor-Cognitive and Aerobic Exercises Rehabilitation Program Multidisciplinary Intensive Rehabilitation Intervention of highly challenging motor and cognitive training for 6 consecutive weeks. Home-Based Stretching Exercises Muscle-stretching and active mobilization exercises Home-based self-treatment program for 40 '/ day for 6 consecutive weeks
- Primary Outcome Measures
Name Time Method Serum biomarkers in neuron derived extracellular vesicles (NDEVs) 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 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.
- Secondary Outcome Measures
Name Time Method IdeoMotor praxis 18 weeks Gesture Imitation Test (IMA-T) \[0-72, 0=worse, 72=better outcome\]
Visuo-spatial memory 18 weeks Rey's Figure - Recall \[0-36, 0=worse, 36=better outcome\]
Balance 18 weeks Modified Dynamic Gait Index (mDGI): The mDGI measure balance skills consists of 8 items and results in a total score of 0 to 64.
Aerobic capacity and endurance 18 weeks 6 Minute Walk Test (6-MWT). The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.
Strenght 18 weeks 5-Time Sit-To-Stand (5TSTS) is based on the amount of time (in seconds) a patient is able to transfer from a seated to a standing position and back to sitting five times.
Non-Motor symptoms 18 weeks Non-Motor Symptoms Scale (NMSS) \[range: 0-360, 0=better outcome, 360=worse outcome\];
Extradimensional non-verbal set-shifting 18 weeks Trail Making Test (TMT) \[0-∞, 0=worse, ∞=better outcome\]
Depression 18 weeks Beck Depression Inventory-II (BDI-II) \[0-63, 0=better, 63=worse outcome\]
Dynamic Balance 18 weeks - Timed-Up and -Go Test (TUG); subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again. The Time (seconds) is measured.
Gait speed 18 weeks 10 Meter Walk Test (10MWT) assess walking speed in meters per second over a distance of 6 meters.
Sleep quality 18 weeks Pittsburgh Sleep Quality Index (PSQI) \[range: 0-21, 0=better outcome, 21=worse outcome\];
Frontal lobe functioning 18 weeks Frontal Assessment Battery (FAB) \[0-18, 0=worse, 18=better outcome\]
Fatigue 18 weeks Parkinson Fatigue Scale (PFS) \[range: 1-5, 1=better outcome, 5=worse outcome\];
Motor and non-motor symptoms 18 weeks The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I-IV.
MDS-UPDRS-PART I ''nonmotor experiences of daily living -nM-EDL-" range: 0-52, 0=better outcome, 52=worse outcome; PART-II ''motor experiences of daily living -M-EDL-'' range: 0-52, 0=better outcome, 52=worse outcome; PART-III ''motor examination'' range: 0-132, 0=better outcome, 132=worse outcome; PART IV ''motor complications'' range: 0-24, 0=better outcome, 24=worse outcome.Daytime sleepiness 18 weeks Epworth Sleepiness Scale (ESS) \[range: 0-24, 0=better outcome, 24=worse outcome\];
Parkinson's disease-specific health related quality of life 18 weeks The Parkinson Disease Questionnaire (PDQ-39) \[PDQ-39 range: 0%-100%; 0%=better outcome, 100%=worse outcome\].
Verbal short-term and working memory 18 weeks Forward and Backward Verbal Span \[0-9, 0=worse, 9=better outcome\]
Cognitive interference inhibition 18 weeks Stroop Test-Short Version \[Error: 0-30, 0=better, 30=worse outcome;Time: range: 0-∞, 0=better, ∞=worse outcome\]
Apathy 18 weeks Dimensional Apathy Scale (I-DAS) \[0-72, 0=better, 72=worse outcome\]
Impulsivity 18 weeks Barratt Impulsiveness Scale-11 (BIS-11) \[30-120, ;30=better, 120=worse outcome\]
Daily self-care activities 18 weeks Activities of Daily Living (ADL) \[0-6, 0=worse, 6=better outcome\] Instrumental Activities Of Daily Living (IADL) \[0-8, 0=worse, 8=better outcome\]
Cerebral blood flow 18 weeks Advanced MRI-3 Tesla protocols, including arterial spin labeling (ASL) to assess the neural correlates of rehabilitation-induced brain plasticity in pwPD undergoing intensive motor and cognitive rehabilitation.
Rapid eye movement sleep behavior disorder 18 weeks REM sleep behavior disorder screening questionnaire (RBDSQ) \[range: 0-13, 0=better outcome, 13=worse outcome\].
Pain Intensity 18 weeks Numeric Rating Scale (NRS) \[range: 0-10, 0=better outcome, 10=worse outcome\];
Global Cognitive Functioning 18 weeks Montreal Cognitive Assessment (MoCA Test)\[0-30, 0=worse, 30=better outcome\] and Mini-Mental Parkinson (MMP)\[0-32, 0=worse, 32=better outcome\]
Gait Analysis 18 weeks Gait analysis will be assessed using a 9-camera SMART-D motion capture system (BTS, Milano, Italy) in order to measure stride length, step width and length, kinematic data and energy recovery.
Language production and non-motor processing speed 18 weeks Verbal fluency test (phonemic and semantic tasks) \[0-∞, 0=worse, ∞=better outcome\]
Anxiety 18 weeks State-Trait Anxiety Inventory. Forma Y (STAI-Y) \[20-80; STAI-Y TRAIT ANXIETY range: 20-80; 20=better, 80=worse outcome\]
Impulsive Control Disorders 18 weeks Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP-RS-IT) \[0-112,; 0=better, 112=worse outcome\]
Autonomic Symptoms 18 weeks Italian version of the Composite Autonomic Symptoms Score (COMPASS-31) \[weighted score range: 0-100, 0=better outcome, 100=worse outcome\];
Verbal episodic memory 18 weeks Immediate and delayed story recall test \[0-8, 0=worse, 8=better outcome; Oblivion Index range: 0-8, 0=worse, 8=better outcome\]
Visuo-constructional ability 18 weeks Rey's Figure - Copy \[0-36, 0=worse, 36=better outcome\]
Non-verbal reasoning 18 weeks Raven Coloured Progressive Matrices (CPM-47) \[0-36, 0=worse, 36=better outcome\]
Extradimensional verbal set-shifting 18 weeks Alternate Verbal Fluency \[0-∞, 0=worse, ∞=better outcome;Shifting Index 0-1, 0=worse, 1=better outcome\]
Speed information processing 18 weeks Symbol Digit Modalities Test (SDMT) (Oral Version) \[0-120, 0=worse, 120=better outcome\]
Anhedonia 18 weeks Snaith-Hamilton Pleasure Scale (SHAPS) \[0-14, 0=better, 14=worse outcome\]
Alexithymia 18 weeks Toronto Alexithymia Scale (TAS-20) \[20-100, 20=better, 100=worse outcome\]
Functional disability 18 weeks Modified Barthel Index (MBI) \[range: 0-100, 0=worse outcome, 100=better outcome\];
Home-based motor activity monitoring 18 weeks The acquisitions will be obtained from the actigraphs (mounted one on the right wrist and the other on the left wrist).
Behavioral disturbances 18 weeks NeuroPsychiatric Inventory Questionnaire (NPI-Q) \[SE: 0-36, 0=better, 36=worse outcome; ST= 0-60, 0=better, 60=worse outcome\]
Caregiver burden 18 weeks Caregiver Burden Inventory (CBI) \[range 0-96, 0=better, 96=worse outcome\]
Brain functional connectivity 18 weeks Advanced Magnetic Resonance Imaging (MRI)-3 Tesla protocols, including resting state functional MRI to assess the neural correlates of rehabilitation-induced brain plasticity in pwPD undergoing intensive motor and cognitive rehabilitation.
Trial Locations
- Locations (1)
IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi
🇮🇹Milan, Italy