Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson's Disease

NCT ID: NCT05452655

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-09
• Study Completion Date: 2023-12-31

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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intensive Outpatient Integrated Motor-Cognitive and Aerobic Exercises Rehabilitation Program

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

Group Type: EXPERIMENTAL

Multidisciplinary Intensive Rehabilitation

Intervention Type: 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).

Home-Based Stretching Exercises

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

Group Type: ACTIVE_COMPARATOR

Muscle-stretching and active mobilization exercises

Intervention Type: 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.

Interventions

Multidisciplinary Intensive Rehabilitation

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).

Intervention Type: BEHAVIORAL

Muscle-stretching and active mobilization exercises

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.

Intervention Type: BEHAVIORAL

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Don Carlo Gnocchi Onlus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario Meloni, MD;PhD

Role: PRINCIPAL_INVESTIGATOR

IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi ONLUS

Locations

IRCCS S. Maria Nascente, Fondazione Don Carlo Gnocchi

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Mario Meloni, MD; PhD

Role: CONTACT

mmeloni@dongnocchi.it

0240308304 ext. +39

Facility Contacts

Mario Meloni, MD; PhD

Role: primary

mmeloni@dongnocchi.it

0240308304 ext. +39

Francesca Lea Saibene, M.Sc.

Role: backup

fsaibene@dongnocchi.it

References

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.

Reference Type: DERIVED

PMID: 39441873 (View on PubMed)

Other Identifiers

11_16/04/2020

Identifier Type: -

Identifier Source: org_study_id