Clinical trial NCT05452655: Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Biomarkers
Rehabilitation Outcome
Gait Disorders, Neurologic
Parkinsonian Disorders
Basal Ganglia Diseases
Central Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Cognitive Impairment
Gait Analysis
Pathologic Processes
Magnetic Resonance Imaging
Physiotherapy
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
First posted: 2022-07-11
Enrollment: 72
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is designed as a Randomized Controlled Trial (RCT). Subjects with a diagnosis of PD in accordance of MDS criteria will be randomly allocated to the experimental (EXP) or control group (CTR).

Clinical, kinematic, blood samples and MRI data will be collected before (T0) at the end of treatment (T1) and 3 months after the end of treatment (T2).
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Serum biomarkers in neuron derived extracellular vesicles (NDEVs)
timeFrame: 18 weeks
measure: Blood Biomarkers
timeFrame: 18 weeks
Secondary outcomes:
measure: Dynamic Balance
timeFrame: 18 weeks
measure: Aerobic capacity and endurance
timeFrame: 18 weeks
measure: Gait speed
timeFrame: 18 weeks
measure: Strenght
timeFrame: 18 weeks
measure: Balance
timeFrame: 18 weeks
measure: Gait Analysis
timeFrame: 18 weeks
measure: Motor and non-motor symptoms
timeFrame: 18 weeks
measure: Non-Motor symptoms
timeFrame: 18 weeks
measure: Fatigue
timeFrame: 18 weeks
measure: Daytime sleepiness
timeFrame: 18 weeks
measure: Sleep quality
timeFrame: 18 weeks
measure: Rapid eye movement sleep behavior disorder
timeFrame: 18 weeks
measure: Autonomic Symptoms
timeFrame: 18 weeks
measure: Pain Intensity
timeFrame: 18 weeks
measure: Parkinson's disease-specific health related quality of life
timeFrame: 18 weeks
measure: Global Cognitive Functioning
timeFrame: 18 weeks
measure: Verbal short-term and working memory
timeFrame: 18 weeks
measure: Verbal episodic memory
timeFrame: 18 weeks
measure: Visuo-constructional ability
timeFrame: 18 weeks
measure: Visuo-spatial memory
timeFrame: 18 weeks
measure: Frontal lobe functioning
timeFrame: 18 weeks
measure: Non-verbal reasoning
timeFrame: 18 weeks
measure: Extradimensional verbal set-shifting
timeFrame: 18 weeks
measure: Extradimensional non-verbal set-shifting
timeFrame: 18 weeks
measure: Speed information processing
timeFrame: 18 weeks
measure: Cognitive interference inhibition
timeFrame: 18 weeks
measure: IdeoMotor praxis
timeFrame: 18 weeks
measure: Language production and non-motor processing speed
timeFrame: 18 weeks
measure: Depression
timeFrame: 18 weeks
measure: Anxiety
timeFrame: 18 weeks
measure: Apathy
timeFrame: 18 weeks
measure: Anhedonia
timeFrame: 18 weeks
measure: Impulsivity
timeFrame: 18 weeks
measure: Alexithymia
timeFrame: 18 weeks
measure: Impulsive Control Disorders
timeFrame: 18 weeks
measure: Behavioral disturbances
timeFrame: 18 weeks
measure: Functional disability
timeFrame: 18 weeks
measure: Daily self-care activities
timeFrame: 18 weeks
measure: Caregiver burden
timeFrame: 18 weeks
measure: Brain functional connectivity
timeFrame: 18 weeks
measure: Cerebral blood flow
timeFrame: 18 weeks
measure: Home-based motor activity monitoring
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi
Study officials:
affiliation: IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi ONLUS
name: Mario Meloni, MD;PhD
role: PRINCIPAL_INVESTIGATOR
References: