Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson's Disease

NCT05452655 | Unknown

• 1 other identifier: 11_16/04/2020
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Serum biomarkers in neuron derived extracellular vesicles (NDEVs)

  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)

  18 weeks

• Blood Biomarkers

  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.

  18 weeks

Secondary Outcomes (42)

• Dynamic Balance

  18 weeks

• Aerobic capacity and endurance

  18 weeks

• Gait speed

  18 weeks

• Strenght

  18 weeks

• Balance

  18 weeks

Study Arms (2)

Intensive Outpatient Integrated Motor-Cognitive and Aerobic Exercises Rehabilitation Program

EXPERIMENTAL

Intervention of highly challenging motor and cognitive training for 6 consecutive weeks.

Behavioral: Multidisciplinary Intensive Rehabilitation

Home-Based Stretching Exercises

ACTIVE COMPARATOR

Home-based self-treatment program for 40 '/ day for 6 consecutive weeks

Behavioral: Muscle-stretching and active mobilization exercises

Interventions

Multidisciplinary Intensive Rehabilitation BEHAVIORAL

The rehabilitation program will last for 6 consecutive weeks and involves the execution of 30 sessions, 5 days a week lasting 160 '/ day each (80' motor; 40 'cognitive and 40' speech therapy rehabilitation) for 3 days a week and 180'/ day (80 'motor; 60' cognitive and 40 'speech therapy rehabilitation) for 2 days a week. The EXP group will receive 18 sessions (3 times a week) of treadmill (20 min), balance exercises and functional reinforcement (20 min). The remaining motor sessions will be defined based on the patient's therapeutic needs. The cognitive treatment will be proposed both in traditional mode (3 times a week) and through the support of semi-immersive "Virtual Reality Rehabilitation System" (VRRS) (2 times/week). The VRRS treatment is structured in 2 sessions per week (60 min) for 6 consecutive weeks. The speech therapy program will include clinical and instrumental evaluations and innovative techniques will be used for the treatment (biofeedback with Vitalstim).

Intensive Outpatient Integrated Motor-Cognitive and Aerobic Exercises Rehabilitation Program

Muscle-stretching and active mobilization exercises BEHAVIORAL

The control group subjects will undergo a home-based self-treatment program for 40 '/ day for 6 consecutive weeks consisting of muscle-stretching and active mobilization exercises.

Home-Based Stretching Exercises

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Don Carlo Gnocchi Onlus: lead

Study Sites (1)

IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi

Milan, 20148, Italy

RECRUITING

Related Publications (1)

• Saibene FL, Agliardi C, Salvatore A, Arcuri P, Castagna A, Gobbo S, Merlo F, Bowman T, Anastasi D, Pagliari C, Farina E, Alberoni M, Calabrese E, La Rosa F, Arienti C, Saresella M, Guerini FR, Cattaneo D, Baglio F, Clerici M, Navarro J, Meloni M. Investigating the effects of a daily multidisciplinary intensive outpatient rehabilitation program on innovative biomarkers in people with Parkinson's disease: Study protocol for a phase III randomized controlled clinical trial. PLoS One. 2024 Oct 23;19(10):e0309405. doi: 10.1371/journal.pone.0309405. eCollection 2024.

  PMID: 39441873 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic; Parkinsonian Disorders; Basal Ganglia Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Pathologic Processes

Condition Hierarchy (Ancestors)

Brain Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Mario Meloni, MD;PhD

  IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi ONLUS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mario Meloni, MD; PhD

CONTACT

0240308304; mmeloni@dongnocchi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: July 11, 2022
• Study Start: December 9, 2020
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 11, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)