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NCT Number: NCT06868160

Comparison of Different Non-invasive Electrical Stimulation Protocols to Facilitate Rehabilitation in Parkinson's Disease Subjects With Postural Instability and Gait Disorders

The trial will include 51 adult participants with Parkinson's disease and postural instability and gait disorders (PD-PIGD) and 20 age- and sex-matched healthy controls.

At baseline (T0) patients will undergo neurological and cognitive/behavioural assessments, gait/balance evaluation, neuroimaging/neurophysiology assessments including brain magnetic resonance imaging (MRI), functional Near Infrared Spectroscopy (fNIRS) and Electroencephalography (EEG) acquisitions to assess brain activity, connectivity and structural changes, and blood sample.

PD-PIGD patients will be randomly allocated in two training groups: the REHAB+SHAM group and the REHAB + STIM group.

The REHAB+SHAM group will perform 2 cycles of dual-task gait/balance training consisting of action observation training (AOT) and motor imagery (MI) combined with practicing the observed-imagined exercises (an approach that has been demonstrated to be effective to improve gait and mobility in PD-PIGD), additionally they will undergo SHAM transcranial and trans-spinal stimulation. SHAM stimulation will be performed using the same montage used for transcranial and spinal stimulation (explained below), however an initial current is delivered and programmed to fade off in a brief period of time.

The REHAB + STIM group will perform the same exercises combined with non-invasive stimulation.

Non-invasive stimulation will be administered using tDCS with trans-spinal Direct Current Stimulation (tsDCS) or transcranial Direct Current Stimulation (tDCS) alone combined with SHAMtsDCS.

This design will aid in determining not only whether non-invasive stimulation can enhance rehabilitation outcomes but also whether the combination of tDCS and tsDCS could lead to improved results compared to tDCS alone.

The motor-cognitive training of the REHAB+SHAM group will consist of 2 cycles of SHAM stimulation and training lasting 6 weeks, 3 times per week, about 1 hour each session, separated by a 8-week washout period.

The REHAB + STIM group will undergo 2 cycles of the 6-week training, separated by a 8-week washout period with a cross-over design: half of subjects will first receive 6-week training with tDCS+SHAMtsDCS followed by 6-week tDCS+ tsDCS, while the other half will follow the reverse order, according to a randomization procedure.

After the training (i.e., 6-week visit [W6] and 20-week visit [W20]), PD-PIGD patients will be re-evaluated through neurological, cognitive/behavioural, gait/balance, neuroimaging/neurophysiology assessments and blood sample.

These measures (except for MRI at 14-week [W14] visit) will be also repeated at W14 and 28-week follow-up visits to assess maintenance of results.

20 healthy controls will also be recruited and evaluated at baseline. They will undergo the same assessments administered to PD-PIGD patients at T0 (neurological, cognitive/behavioural assessments, gait/balance evaluation using gait analysis systems, neuroimaging/neurophysiology, blood sample).

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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

San Raffaele Neurotech Hub

Milan, 20132, Italy

Location status: Recruiting

Location contact

Massimo Filippi, Prof., MD

CONTACT

[email protected]

0226433054 ext. 0039

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • 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

Healthy controls' inclusion criteria:

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

Exclusion criteria

  • Any major systemic, psychiatric, neurological, visual, and musculoskeletal disturbances or other causes of walking inability
  • Medical conditions or substance abuse that could interfere with cognition
  • Pacemaker or other implanted neurostimulation devices in the head/neck district
  • (Other) Contraindications to undergoing MRI examination
  • Brain damage at routine MRI, including extensive cerebrovascular disorders
  • Denied oral and written informed consent to study participation
  • Significant scalp traumatic or surgical wounds or scalp alterations that could determine a risk of infection in the site of non-invasive stimulation or the spread of excessive current from the device (only for patients receiving the neurostimulation).

Treatment and study plan

Rehabilitation

Behavioral

Two cycles of dual-task gait/balance training consisting of action observation training (AOT) and motor imagery (MI) combined with practicing the observed-imagined exercises.

Three 1-hour sessions per week for 6 weeks. Cycle repeated after 8-week washout period.

Sham tDCS

Device

SHAM stimulation will be performed using the same montage used for transcranial and spinal stimulation, however an initial current is delivered and programmed to fade off in a brief period of time.

tDCS

Device

Anodic tDCS with the anode placed on the of the left DorsoLateral Prefrontal Cortex. Patients will undergo 30 minutes tDCS session preceding rehabilitation

tsDCS (first cycle)

Device

Anodic spinal cervical stimulation with anode electrode placed on the spinous process of C3 vertebra and cathode placed on T3. Patients will undergo 30 minutes stimulation session preceding rehabilitation during the first cycle (6 weeks)

tsDCS (second cycle)

Device

Anodic spinal cervical stimulation with anode electrode placed on the spinous process of C3 vertebra and cathode placed on T3. Patients will undergo 30 minutes stimulation session preceding rehabilitation during the second cycle (6 weeks after 8-week washout)

SHAM tsDCS (first cycle)

Device

SHAM stimulation will have the same montage as tsDCS but run in SHAM more with an initial stimulation at standard intensity, followed by a programmed fade off after a brief time period. Patients will undergo 30 minutes of SHAM stimulation session preceding rehabilitation during the first cycle (6 weeks)

SHAM tsDCS (second cycle)

Device

SHAM stimulation will have the same montage as tsDCS but run in SHAM more with an initial stimulation at standard intensity, followed by a programmed fade off after a brief time period. Patients will undergo 30 minutes of SHAM stimulation session preceding rehabilitation during the second cycle (6 weeks after 8-week washout)

SHAM tsDCS

Device

SHAM stimulation will have the same montage as tsDCS but run in SHAM more with an initial stimulation at standard intensity, followed by a programmed fade off after a brief time period. Patients will undergo 30 minutes of SHAM stimulation session preceding rehabilitation

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, week 20 and week 28

    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, week 20 and week 28

    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, week 20 and week 28

    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, week 20 and week 28

    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, week 20 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. Changes at resting-state functional Near-Infrared Spectroscopy (fNIRS)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    Changes in the continuous spectral wave of brain resting activity

  6. Changes in Electroencephalography (EEG) signal

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    Changes in electrical brain activity during resting with eyes open and eyes closed

  7. Serum concentration of Neurofilament light chain (NfL)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    Serum biomarker of neuroprotection/neurodegeneration

  8. Activity Balance Confidence questionnaire (ABC) score

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

  9. 10-meter walk test (10MWT) time

    Time frame: Baseline, week 6, week 14, week 20 and week 28

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

  10. Mini Balance Evaluation System Test (MiniBESTest) score

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

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

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

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

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

  13. Kinesthetic and Visual Imagery Questionnaire (KVIQ)

    Time frame: Baseline, week 6, week 14, week 20 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.

  14. Vividness of Movement imagery Questionnaire (VMIQ)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    This questionnaire measures vividness of imagery in different visual imagery modalities (first and third person view) and kinaesthetic modality.

    Patients, for each imagery modality, give a score from 1 (best) to 5 (worse) to the clarity/intensity of 12 imagined actions.

  15. Parkinson Fatigue Scale (PFS)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    Patient-rated scale that reflects the physical aspects of fatigue in patients with Parkinson's Disease (PD) and measures both the presence of fatigue and its impact on daily function

  16. Fatigue Severity Scale (FSS)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle

  17. Modified Fatigue Impact Scale (M-FIS)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    Provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning

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

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

  19. Stride length

    Time frame: Baseline, week 6, week 14, week 20 and week 28

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

  20. Gait velocity

    Time frame: Baseline, week 6, week 14, week 20 and week 28

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

  21. Cambridge Neuropsychological Test Automated Battery (CANTAB)

    Time frame: Baseline, week 6, week 14, week 20 and week 28

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Elisabetta Sarasso, MSc

CONTACT

[email protected]

0226434685 ext. 0039

Federica Agosta, PhD, MD

CONTACT

[email protected]

0226433051 ext. 0039

Sponsors and collaborators

Lead sponsor

IRCCS San Raffaele

Other

Registry information

Official study title

Neurotech PD Gait: Multisite Non-invasive Electrical Stimulation to Optimize Motor-cognitive Rehabilitation Response in Parkinson's Disease Subjects With Postural Instability and Gait Disorders

Important dates

Study start
2025
Primary completion
2028
Study completion
2029
First posted
Mar 10, 2025
Registry last updated
Dec 3, 2025

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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