Clinical trial NCT06868160: Comparison of Different Non-invasive Electrical Stimulation Protocols to Facilitate Rehabilitation in Parkinson's Disease Subjects With Postural Instability and Gait Disorders
Official 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Gait
Rehabilitation
Biomarkers
Magnetic Resonance Imaging
Functional Near Infrared Spectroscopy
Non-invasive Electrical Stimulation
Electroencephalogram
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2025-03-10
Enrollment: 71
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: SUPPORTIVE_CARE

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).


Eligibility criteria: Inclusion Criteria:

* 45 years \&lt; age ≤ 85 years
* Idiopathic PD according to the Movement Disorders Society (MDS) diagnostic criteria
* Hoehn \&amp; Yahr (H\&amp;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\&#39;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).

Primary outcomes:
measure: Total execution time of Timed Up and Go test with cognitive dual-task (TUG-COG)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
Secondary outcomes:
measure: Total execution time of Timed Up and Go test (TUG)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Total execution time of Timed Up and Go test with manual dual-task (TUG-MAN)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Brain functional changes during functional magnetic resonance imaging (MRI) tasks
timeFrame: Baseline, week 6, week 20 and week 28
measure: Changes at resting-state functional Near-Infrared Spectroscopy (fNIRS)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Changes in Electroencephalography (EEG) signal
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Serum concentration of Neurofilament light chain (NfL)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Activity Balance Confidence questionnaire (ABC) score
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: 10-meter walk test (10MWT) time
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Mini Balance Evaluation System Test (MiniBESTest) score
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Five-time sit-to-stand (5STS) time
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Parkinson's Disease Questionnaire (PDQ-39) score
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Kinesthetic and Visual Imagery Questionnaire (KVIQ)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Vividness of Movement imagery Questionnaire (VMIQ)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Parkinson Fatigue Scale (PFS)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Fatigue Severity Scale (FSS)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Modified Fatigue Impact Scale (M-FIS)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: New Freezing of Gait Questionnaire (NFoG-Q)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Stride length
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Gait velocity
timeFrame: Baseline, week 6, week 14, week 20 and week 28
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: Baseline, week 6, week 14, week 20 and week 28
Other outcomes:
Locations:
city: Milan
country: Italy
facility: San Raffaele Neurotech Hub
Study officials:
References: