Clinical trial NCT05092243: Exploit the Functional Higher Neural Connectivity and Electrophysiological Intervention of Freezing of Gait in PD and PSP During Different Ambulatory Complexities
Official title: Exploit the Functional Higher Neural Connectivity and Electrophysiological Intervention of Freezing of Gait in Parkinson's Disease and Supranuclear Palsy During Different Ambulatory Complexities
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Transcranial Direct Current Stimulation
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Taiwan
First posted: 2021-10-25
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: In the current proposal, investigators will investigate three crucial issues of FOG. Firstly, investigators will identify the possible source(s) of FOG in PD and PSP patients during unconstrained walking using a 64-channel ambulatory recorder. The investigators will explore the electric neural sources of FOG and brain connectivity. Secondarily, fMRI during motor imagery will be performed to examine the brain regions involved in the FOG patients. The investigators will merge the electrophysiological and imaging findings to detect the possible neurovascular coupling or uncoupling. Thirdly, electric intervention with transcranial direct current stimulation (tDCS) will be conducted to see whether the FOG situation can be ameliorated in PD and PSP patients. The investigators will deliver a 5-day session of tDCS to the leg motor cortex of the FOG patients to examine whether the intervention will benefit the patients in a double blind randomized design. Six assessments with different combinations of clinical scaling, gait analysis, electrophysiological investigation and fMRI examinations before and after tDCS will be conducted. Besides, there is no long-term cohort investigation of tDCS on neurodegenerative patients with FOG. The investigators will have a 3-year follow-up with a 1-month interval open-label stimulation paradigm for the patients who remained voluntarily after the termination of the initial short-term trials.

Detailed description: The main goal of the first part of the 3-year project is to identify the source(s) of FOG with electrophysiological recording. The investigators will conduct concomitant high density Electroencephalographic and leg electromyographic recording to investigate subjects with and without FOG under unrestrained walking in the gait laboratory. The acquisitive signals from 64 montages will be decomposed first by independent component analysis (ICA) for further source localization of FOG. The event (FOG) related synchronization and desynchronization of different frequency bands of EEG will also be investigated to understand the neurophysiological implications of brain wave oscillations for the generation of FOG. In addition, the cerebello-thalamo-cortical pathway function will be assessed with magnetic paired associative stimulation in patients to probe the role of cerebellum in the pathogenesis of FOG. In the second part of the project, fMRI study will be adopted by having the subjects perform video-guided motor imagery of simple and complex walking situations. Block design paradigms will be delivered for signal acquisition. The signals will be analyzed by ICA before further processing for activation analysis. The connectivity map will beoverlaid with that of electric recording to examine the neurovascular coupling or uncoupling. In the third part of the project, investigators will deliver a 5-day session of transcranial direct current stimulation (tDCS) to the leg motor cortex of the FOG patients to examine whether the intervention will benefit the patients in a doubleblind randomized cross-over design.

Eligibility criteria: Inclusion Criteria:

Patients meet the diagnosis of PD or PSP based on the established consensus criteria

Exclusion Criteria:

1. Impairment of cognition that leads unable to fully cooperate with the oral commands during examinations
2. Functional III or above congestive heart failure, or cancer with distant metastasis
3. Hoehn and Yahr stage 5 in PD or PSP

Primary outcomes:
measure: Electroencephalogram recording before and after the tDCS session
timeFrame: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
measure: Electromyography recording before and after the tDCS session
timeFrame: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
measure: Functional magnetic resonance images examination before and after the tDCS session
timeFrame: baseline / 2 days after the end of the tDCS session
Secondary outcomes:
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III before and after the tDCS session
timeFrame: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
measure: Change in Progressive Supranuclear Palsy Rating Scale (PSPRS)
timeFrame: baseline / 2 days, 2 and 4 weeks after the end of the tDCS session
Other outcomes:
measure: Change in New freezing of gait questionnaire (NFOG-Q) before and after the tDCS session
timeFrame: baseline / 4 weeks after the end of the tDCS session
measure: Change in Tinetti's Mobility Index total score before and after the tDCS session
timeFrame: baseline / 4 weeks after the end of the tDCS session
measure: Change inParkinson's Disease Questionnaire 39 (PDQ-39) before and after the tDCS session
timeFrame: baseline / 4 weeks after the end of the tDCS session
measure: Non-Motor Symptoms Questionnaire (NMSQ)
timeFrame: baseline / 4 weeks after the end of the tDCS session
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital/Neuro Depart
Study officials:
affiliation: The chief, Department of Neurology, China Medical University Hospital
name: Chon-Haw Tsai, PHD
role: PRINCIPAL_INVESTIGATOR
References: