Comparison of Different Rehabilitation Protocols in Parkinson's Disease With Postural Instability and Gait Disorders

NCT05799690 | Active Not Recruiting DMC

• 1 other identifier: GR-2021-12374005
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of the study is to compare the effects of 2 different dosages and modalities of motor-cognitive rehabilitation in Parkinson's disease with postural instability and gait disorders (PD-PIGD) on clinical features, neuroimaging and blood-based biomarkers at short-term (2 months) and long-term (7 months) follow-up. Fifty subjects with PD-PIGD will be randomized in 2 training groups: DUAL-TASK+AOT-MI and the DUAL-TASK groups. The DUAL-TASK+AOT-MI group will perform a dual-task gait/balance training consisting of action observation training (AOT) and motor imagery (MI) combined with practicing the observed-imagined exercises; DUAL-TASK group will perform the same exercises combined with watching landscape videos. The training will last 6 weeks, 3 times/week, 1 hour per session. Before and after training (W6), all the patients will undergo neurological, gait/balance, cognitive/behavioral, magnetic resonance imaging (MRI) and serum biomarkers evaluations. Neurological, gait/balance, cognitive/behavioral assessments and serum biomarkers will be also repeated at the 14-week follow-up (W14) to assess maintenance of results. Patients of both DUAL-TASK+AOT-MI and DUAL-TASK groups will be further randomized to repeat the training (6 weeks, 3 times/week, 1 hour each session) starting at W14 (DUAL-TASK+AOT-MI\_DOUBLE and DUAL-TASK\_DOUBLE groups). After six weeks (W20) all the subjects repeating the training will be evaluated (neurological, gait/balance, cognitive/behavioral assessments). At 28-week follow-up (W28), the whole sample of patients will be assessed with neurological, gait/balance, cognitive/behavioral, MRI and serum biomarkers evaluations. All MRI scans will be acquired at least 12 hours after last dopaminergic therapy administration to mitigate the pharmacological effects on neural activity. Twenty age- and sex-matched healthy controls will be recruited to perform gait/balance and cognitive/behavioral assessments, blood sample and brain MRI acquisition at baseline. The secondary aims of the study are to define the neuroimaging and blood-based biomarkers of PD-PIGD patients presenting different clinical features (e.g. presence of mild cognitive impairment, freezing of gait, falls and mood disturbances) and to evaluate the role of blood-based and neuroimaging biomarkers, together with clinical characteristics, in predicting the response to different dosages of rehabilitation in PD-PIGD throughout the development of a machine-learning algorithm.

Conditions

Parkinson Disease

Keywords

Parkinson Disease; Gait; Rehabilitation; Biomarkers; Magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)

  Changes in time taken to complete the timed up and go test with cognitive dual-task: patients are asked to stand up from a chair, walk for three meters, turn and walk back to the chair while counting backwards by 3 starting from 100. Assessment during ON medication phase.

  Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.

Secondary Outcomes (22)

• Total execution time of Timed Up and Go test (TUG)

  Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.

• Total execution time of Timed Up and Go test with manual dual-task (TUG-MAN)

  Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.

• Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score

  Baseline, week 6, week 14 and week 28. At week 20 only for patients repeating the training.

• Brain functional changes during functional magnetic resonance imaging (MRI) tasks

  Baseline, week 6 and week 28

• Serum concentration of Neurofilament light chain (NfL)

  Baseline, week 6, week 14 and week 28.

Study Arms (5)

DUAL-TASK+AOT-MI

EXPERIMENTAL

Dual-task gait and balance training with cognitive facilitations (action observation and motor imagery) for six weeks.

Behavioral: Gait and balance training with dual-task + action observation and motor imagery (six weeks)

DUAL-TASK

ACTIVE COMPARATOR

Dual-task gait and balance training with vision of landscape videos for six weeks.

Behavioral: Gait and balance training with dual-task (six weeks)

DUAL-TASK+AOT-MI_DOUBLE

EXPERIMENTAL

Dual-task gait and balance training with cognitive facilitations (action observation and motor imagery) repeated two times (twelve weeks: 6 + 6).

Behavioral: Gait and balance training with dual-task + action observation and motor imagery (twelve weeks: 6 + 6)

DUAL-TASK_DOUBLE

ACTIVE COMPARATOR

Dual-task gait and balance training with vision of landscape videos repeated two times (twelve weeks: 6 + 6).

Behavioral: Gait and balance training with dual-task (twelve weeks: 6 +6)

Healthy subjects

NO INTERVENTION

Age- and sex-matched healthy subjects recruited to compare gait, neuropsychological, serum and functional magnetic resonance imaging characteristics at baseline.

Interventions

Gait and balance training with dual-task + action observation and motor imagery (six weeks) BEHAVIORAL

Increasingly difficult gait and balance exercises up to include dual-task. During each training session, four exercises (5 minutes of execution, two times each) will be proposed. Patients will observe a 2-minute video clip showing a balance or gait task (action observation - AOT) and will imagine the same exercise (motor-imagery - MI) before task execution. Each training session will be proposed with the following modality: 2 minutes of AOT - 5 minutes of task execution - 2 minutes of MI - 5 minutes of task execution. Patients will be explicitly asked to concentrate on how the actions are performed in the videos and to carefully use MI to improve their motor performance. Patients will not be allowed to perform any movement while watching videos or during MI. 1 hour, 3 times a week for six weeks.

DUAL-TASK+AOT-MI

Gait and balance training with dual-task (six weeks) BEHAVIORAL

Increasingly difficult gait and balance exercises up to include dual-task. During each training session, four exercises (5 minutes of execution, two times each) will be proposed. Patients will observe a 2-minute video clip showing static landscapes before task execution. Each training session will be proposed with the following modality: 2 minutes of videos - 5 minutes of task execution - 2 minutes of videos - 5 minutes of task execution. 1 hour, 3 times a week for six weeks.

DUAL-TASK

Gait and balance training with dual-task + action observation and motor imagery (twelve weeks: 6 + 6) BEHAVIORAL

Increasingly difficult gait and balance exercises up to include dual-task. During each training session, four exercises (5 minutes of execution, two times each) will be proposed. Patients will observe a 2-minute video clip showing a balance or gait task (action observation - AOT) and will imagine the same exercise (motor-imagery - MI) before task execution. Each training session will be proposed with the following modality: 2 minutes of AOT - 5 minutes of task execution - 2 minutes of MI - 5 minutes of task execution. Patients will be explicitly asked to concentrate on how the actions are performed in the videos and to carefully use MI to improve their motor performance. Patients will not be allowed to perform any movement while watching videos or during MI. The training protocol will be repeated two times: once starting at baseline, once starting after the first follow-up at week 14 (W14) 1 hour, 3 times a week for twelve weeks (6+6).

DUAL-TASK+AOT-MI_DOUBLE

Gait and balance training with dual-task (twelve weeks: 6 +6) BEHAVIORAL

Increasingly difficult gait and balance exercises up to include dual-task. During each training session, four exercises (5 minutes of execution, two times each) will be proposed. Patients will observe a 2-minute video clip showing static landscapes before task execution. Each training session will be proposed with the following modality: 2 minutes of videos - 5 minutes of task execution - 2 minutes of videos - 5 minutes of task execution. The training protocol will be repeated two times: once starting at baseline, once starting after the first follow-up at week 14 (W14) 1 hour, 3 times a week for twelve weeks (6+6).

DUAL-TASK_DOUBLE

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years ≤ age ≤ 85 years;
• Idiopathic PD according to the Movement Disorders Society (MDS) diagnostic criteria
• Hoehn \& Yahr (H\&Y) score \<= 4
• PIGD phenotype
• Stable dopaminergic medication for at least 4 weeks and without any changes during the observation period (28 weeks)
• No dementia according to Litvan's criteria and Mini-Mental Status Examination score (MMSE) \>= 24
• No significant tremor/involuntary movements that could determine artifacts during the MRI acquisition
• Oral and written informed consent to study participation
• sex-matched and age-matched (age range: mean age of PD years ± 15 years);
• oral and written informed consent to study participation

You may not qualify if:

• Medical conditions or substance abuse that could interfere with cognition;
• Any major systemic, psychiatric, neurological, visual, and musculoskeletal disturbances or other causes of walking inability;
• Contraindications to undergoing MRI examination;
• Brain damage at routine MRI, including lacunae and extensive cerebrovascular disorders;
• Denied oral and written informed consent to study participation.

Sponsors & Collaborators

• Prof. Massimo Filippi: lead
• Azienda Ospedaliera Universitaria Integrata Verona: collaborator

Study Sites (2)

IRCCS San Raffaele

Milan, 20132, Italy

Location

Neurology Unit, Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37126, Italy

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Gait

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Walking; Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Physiotherapist, neurologists, neuropsychologists and radiologist assessing the patients are blinded to group allocation.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Model Details: Single-blind randomized controlled trial. Fifty PD patients are randomly divided into two groups: 25 in DUAL-TASK+AOT-MI (experimental) and 25 in the DUAL-TASK (active comparator). Half of the patients are further randomized to repeat the treatment (DUAL-TASK+AOT-MI\_DOUBLE and DUAL-TASK\_DOUBLE). The assessors are blinded to the group allocation. In addition, a group of 20 healthy age- and sex-matched control is included at baseline

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: April 5, 2023
• Study Start: April 30, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): April 28, 2027
• Last Updated: March 9, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)