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

NCT06868160 | Recruiting DMC

• 1 other identifier: NEUROTECH_001 PD gait
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

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).

Conditions

Parkinson Disease

Keywords

Parkinson Disease; Gait; Rehabilitation; Biomarkers; Magnetic Resonance Imaging; Functional Near Infrared Spectroscopy; Non-invasive Electrical Stimulation; Electroencephalogram

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, week 20 and week 28

Secondary Outcomes (21)

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

  Baseline, week 6, week 14, week 20 and week 28

• 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

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

  Baseline, week 6, week 14, week 20 and week 28

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

  Baseline, week 6, week 20 and week 28

• Changes at resting-state functional Near-Infrared Spectroscopy (fNIRS)

  Baseline, week 6, week 14, week 20 and week 28

Study Arms (4)

REHAB+SHAM

ACTIVE COMPARATOR

Dual-task gait/balance training consisting of action observation training (AOT) and motor imagery (MI) combined with practicing the observed-imagined exercises. Patients will receive SHAM stimulation.

Behavioral: Rehabilitation; Device: SHAM tDCS; Device: SHAM tsDCS

REHAB+tDCS+tsDCS

EXPERIMENTAL

Patients will perform the same exercises as REHAB+SHAM group, combined with non-invasive stimulation. Non-invasive stimulation will be administered using tDCS (DorsoLateral Prefrontal Cortex) combined with tsDCS for the first cycle (6 weeks). During the second cycle (6 weeks after 8-week washout) patients will receive tDCS + sham tsDCS.

Behavioral: Rehabilitation; Device: tDCS; Device: tsDCS (first cycle); Device: SHAM tsDCS (second cycle)

REHAB+tDCS+SHAMtsDCS

ACTIVE COMPARATOR

Patients will perform the same exercises as REHAB+SHAM group, combined with non-invasive stimulation. Non-invasive stimulation will be administered using tDCS (DorsoLateral Prefrontal Cortex) combined with SHAM tsDCS for the first cycle (6 weeks). During the second cycle (6 weeks after 8-week washout) patients will receive tDCS + tsDCS.

Behavioral: Rehabilitation; Device: tDCS; Device: tsDCS (second cycle); Device: SHAM tsDCS (first cycle)

Healthy subjects

NO INTERVENTION

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

Interventions

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.

REHAB+SHAM

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

REHAB+tDCS+SHAMtsDCS; REHAB+tDCS+tsDCS

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)

REHAB+tDCS+tsDCS

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)

REHAB+tDCS+SHAMtsDCS

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)

REHAB+tDCS+SHAMtsDCS

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)

REHAB+tDCS+tsDCS

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

REHAB+SHAM

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.

REHAB+SHAM; REHAB+tDCS+SHAMtsDCS; REHAB+tDCS+tsDCS

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:

• 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).

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

San Raffaele Neurotech Hub

Milan, 20132, Italy

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Rehabilitation; Transcranial Direct Current Stimulation

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)

Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Federica Agosta, PhD, MD

CONTACT

0226433051; agosta.federica@hsr.it

Elisabetta Sarasso, MSc

CONTACT

0226434685; sarasso.elisabetta@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The assessor blinded will be neurologists, neuropsychologists and physiotherapists who will perform the evaluations at each time point. Patients will not know if they are receiving sham or real stimulation.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Every patient will undergo two rounds of training (6 weeks) with a 8-week washout period in between. Patients will be randomized in two parallel groups: 1/3 of the patients will receive two rounds of rehabilitation + SHAM stimulation; 2/3 of the patients will receive two rounds of rehabilitation + non-invasive STIMULATION. Patients in the STIMULATION group will be further randomized in two groups both receiving tDCS stimulation combined with tsDCS or SHAMtsDCS in a crossover design: one group will receive a first round of rehabilitation + tDCS + tsDCS followed by a round of rehabilitation + tDCS + SHAM tsDCS; the other group will receive the same treatment in an inverted order.

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 10, 2025
• Study Start: October 8, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)