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

Fondazione Don Carlo Gnocchi Onlus1 site in 1 country72 target enrollmentDecember 9, 2020

ConditionsParkinson 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

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Parkinson Disease
Sponsor: Fondazione Don Carlo Gnocchi Onlus
Enrollment: 72
Locations: 1
Primary Endpoint: Serum biomarkers in neuron derived extracellular vesicles (NDEVs)
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

December 9, 2020

End Date

December 2023

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Fondazione Don Carlo Gnocchi Onlus

Responsible Party

Sponsor

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.

Outcomes

Primary Outcomes

Serum biomarkers in neuron derived extracellular vesicles (NDEVs)

Time Frame: 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

Time Frame: 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.