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

San Donato Group (GSD)

Status: Enrolling

Conditions: Parkinson Disease

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06868160

NEUROTECH_001 PD gait

Details and patient eligibility

About

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).

Enrollment: 71 estimated patients

Sex: All

Ages: 45 to 85 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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71 participants in 4 patient groups

REHAB+SHAM

Active Comparator group

Description:

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.

Treatment:

Behavioral: Rehabilitation

Device: SHAM tsDCS

Device: SHAM tDCS

REHAB+tDCS+tsDCS

Experimental group

Description:

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.

Treatment:

Behavioral: Rehabilitation

Device: SHAM tsDCS (second cycle)

Device: tDCS

Device: tsDCS (first cycle)

REHAB+tDCS+SHAMtsDCS

Active Comparator group

Description:

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.

Treatment:

Behavioral: Rehabilitation

Device: tDCS

Device: SHAM tsDCS (first cycle)

Device: tsDCS (second cycle)

Healthy subjects

No Intervention group

Description:

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