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NCT Number: NCT05799690

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

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.

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Key information

Conditions

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

Age range

45 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

IRCCS San Raffaele, Milan, Italy

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for PD patients:

  • 45 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

Inclusion criteria

for healthy controls:

  • sex-matched and age-matched (age range: mean age of PD years ± 15 years);
  • oral and written informed consent to study participation

Exclusion criteria

  • 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.

Treatment and study plan

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.

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.

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).

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).

Primary outcomes

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

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

    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.

Secondary outcomes

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

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

    Changes in time taken to complete the timed up and go test: patients are asked to stand up from a chair, walk for three meters, turn, and walk back to the chair. Assessment during ON medication phase

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

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

    Changes in time taken to complete the timed up and go test with manual dual-task: patients are asked to stand up from a chair, walk for three meters, turn, and walk back to the chair while holding a glass full of water. Assessment during ON medication phase

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

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

    MDS-UPDRS evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. The MDS-UPDRS contains 65 items divided in four parts (Part I - "non-motor experiences of daily living", Part II - "motor experiences of daily living", Part III - "motor examination", Part IV - "motor complications. Each item is assessed with a 0 to 4 rating system. The total score ranges from 0 to 260 with higher score indicating more severe symptoms.

    Assessment during ON medication. Only part III assessed also without medication (OFF).

  4. Brain functional changes during functional magnetic resonance imaging (MRI) tasks

    Time frame: Baseline, week 6 and week 28

    Changes in functional MRI brain activity assessed during a motor task, a cognitive task and a dual-task. Assessment during OFF medication phase, at least 12 hours after last medication assumption.

  5. Serum concentration of Neurofilament light chain (NfL)

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  6. Serum concentration of Glial Fibrillary Acid Protein (GFAP)

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  7. Serum concentration of Phosphorylated Tau (P-Tau)

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  8. Serum concentration of Tau

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  9. Serum concentration of B42

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  10. Serum concentration of B40

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  11. Serum concentration of Alpha-synuclein

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  12. Serum concentration of Brain Derived Neurotrophic Factor (BDNF)

    Time frame: Baseline, week 6, week 14 and week 28.

    Serum biomarker of neuroprotection/neurodegeneration

  13. Activity Balance Confidence questionnaire (ABC) score

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

    This questionnaire assesses patient-referred balance confidence during 16 daily tasks. Subjects rate their confidence while doing each activity from 0 (no confidence) to 100 (full confidence).

    Assessment during ON medication phase.

  14. 10-meter walk test (10MWT) time

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

    Time taken to walk 10 straight meters. Test performed at comfortable and maximal speed. Assessment during ON medication phase.

  15. Mini Balance Evaluation System Test (MiniBESTest) score

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

    Assessment of different balance systems (anticipatory, reactive postural control, sensory orientation, dynamic gait). MiniBESTest includes 14 items with a score from 0 (severe/unable) to 2 (normal). The maximum score is 28 and a higher score indicates a better balance.

    Assessment during ON medication phase.

  16. Five-time sit-to-stand (5STS) time

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

    This test measures the amount of time it takes for a patient to stand up and sit down five times in a row, as quickly as possible with arms folded across their chest. Assessment during ON medication phase.

  17. Parkinson's Disease Questionnaire (PDQ-39) score

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

    Parkinson's Disease Questionnaire investigates the quality of life of PD patients. It includes 39 questions with 5 possible answers (never, occasionally, sometimes, often, always) and 8 sub-items related to mobility, activities of daily living, emotional well-being, signs of discouragement, social support, cognitions, communication and bodily discomfort. The maximum score is 100 and a low score is an indicator of a good quality of life. Assessment during ON medication phase.

  18. Stride length

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

    Gait parameter obtained using wearable motion sensors. Assessment during ON medication phase.

  19. Gait velocity

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

    Gait parameter obtained using wearable motion sensors. Assessment during ON medication phase.

  20. Cambridge Neuropsychological Test Automated Battery (CANTAB)

    Time frame: Baseline, week 6, week 14 and week 28. At week 20 only for patients

    This battery of cognitive tests assesses executive functions, memory and visuospatial abilities.

    Each subtest of the CANTAB battery provides outcome measures in terms of accuracy (right answers, errors and/or missing answers) and reaction times (highest scores are worse) for every condition within the subtest (the different conditions present with different levels of cognitive load). Assessment during ON medication phase.

  21. Kinesthetic and Visual Imagery Questionnaire (KVIQ)

    Time frame: Baseline, week 6 and week 28.

    This questionnaire assesses motor imagery abilities. The Kinesthetic and Visual Imagery Questionnaire (KVIQ) includes 10 items assessing the clarity of the image and the intensity of the sensations that the subject is able to imagine from the first-person perspective (both right and left sides) on a five-point ordinal scale. Total score ranges from 0 to 50 with higher score indicating better motor imagery abilities. Assessment during ON medication phase.

  22. New Freezing of Gait Questionnaire (NFoG-Q)

    Time frame: Baseline, week 6, week 14 and week 28. At week 20 only for patients

    This is a self-reported questionnaire that measures freezing of gait. It consists of 9 items with a total score ranging from 0 (no freezing) to 28. Higher score indicates worse freezing. Assessment during ON medication phase.

Sponsors and collaborators

Lead sponsor

Prof. Massimo Filippi

Other

Collaborators

  • Azienda Ospedaliera Universitaria Integrata Verona

Registry information

Official study title

Multiparametric Biomarkers to Predict the Response to Different Protocols of Motor-cognitive Rehabilitation in Parkinson's Disease Subjects With Postural Instability and Gait Disorders

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Apr 5, 2023
Registry last updated
Mar 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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