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

Overview

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).

Interventions

• Behavioral Rehabilitation
  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.
• Device SHAM tDCS
  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.
• Device tDCS
  Anodic tDCS with the anode placed on the of the left DorsoLateral Prefrontal Cortex. Patients will undergo 30 minutes tDCS session preceding rehabilitation
• Device tsDCS (first cycle)
  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)
• Device tsDCS (second cycle)
  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)
• Device SHAM tsDCS (first cycle)
  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)
• Device SHAM tsDCS (second cycle)
  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)
• Device SHAM tsDCS
  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 outcome measures

• 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]

Secondary outcome measures (12)

• Total execution time of Timed Up and Go test (TUG) [Time frame: 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) [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Brain functional changes during functional magnetic resonance imaging (MRI) tasks [Time frame: Baseline, week 6, week 20 and week 28]
• Changes at resting-state functional Near-Infrared Spectroscopy (fNIRS) [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Changes in Electroencephalography (EEG) signal [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Serum concentration of Neurofilament light chain (NfL) [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Activity Balance Confidence questionnaire (ABC) score [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• 10-meter walk test (10MWT) time [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Mini Balance Evaluation System Test (MiniBESTest) score [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Five-time sit-to-stand (5STS) time [Time frame: Baseline, week 6, week 14, week 20 and week 28]
• Parkinson's Disease Questionnaire (PDQ-39) score [Time frame: Baseline, week 6, week 14, week 20 and week 28]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Supportive care

Study locations

Italy · 1 center

• San Raffaele Neurotech Hub — Milan

Identifiers

NCT: NCT06868160 · NEUROTECH_001 PD gait

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗