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

Not Applicable

Not yet recruiting

• Conditions: Parkinson Disease

• Registration Number: NCT06868160
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-05
• Study First Posted: 2025-03-10
• Status Verified: 2025-04
• Study Start: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Primary Completion: 2028-10
• Study Completion: 2029-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 71

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)	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 Outcome Measures

Name	Time	Method
Total execution time of Timed Up and Go test (TUG)	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
Total execution time of Timed Up and Go test with manual dual-task (TUG-MAN)	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
Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score	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).
Brain functional changes during functional magnetic resonance imaging (MRI) tasks	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.
Changes at resting-state functional Near-Infrared Spectroscopy (fNIRS)	Baseline, week 6, week 14, week 20 and week 28	Changes in the continuous spectral wave of brain resting activity
Changes in Electroencephalography (EEG) signal	Baseline, week 6, week 14, week 20 and week 28	Changes in electrical brain activity during resting with eyes open and eyes closed
Serum concentration of Neurofilament light chain (NfL)	Baseline, week 6, week 14, week 20 and week 28	Serum biomarker of neuroprotection/neurodegeneration
Activity Balance Confidence questionnaire (ABC) score	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.
10-meter walk test (10MWT) time	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.
Mini Balance Evaluation System Test (MiniBESTest) score	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.
Five-time sit-to-stand (5STS) time	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.
Parkinson's Disease Questionnaire (PDQ-39) score	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.
Kinesthetic and Visual Imagery Questionnaire (KVIQ)	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.
Vividness of Movement imagery Questionnaire (VMIQ)	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.
Parkinson Fatigue Scale (PFS)	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
Fatigue Severity Scale (FSS)	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
Modified Fatigue Impact Scale (M-FIS)	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
New Freezing of Gait Questionnaire (NFoG-Q)	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.
Stride length	Baseline, week 6, week 14, week 20 and week 28	Gait parameter obtained using wearable motion sensors. Assessment during ON medication phase.
Gait velocity	Baseline, week 6, week 14, week 20 and week 28	Gait parameter obtained using wearable motion sensors. Assessment during ON medication phase.
Cambridge Neuropsychological Test Automated Battery (CANTAB)	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.

Trial Locations

Locations (1)

San Raffaele Neurotech Hub; 🇮🇹 Milan, Italy