This study aims to explore the therapeutic effects of noninvasive deep brain electrical stimulation using temporal interference principles (Temporal Interference Stimulation, TIS) on both motor and non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes, and to investigate strategies for optimal stimulation target selection. A prospective, single-center, double-blind, randomized, crossover design will be implemented. Participants will be recruited from outpatient and inpatient departments of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. The primary hypothesis is that TIS will significantly improve motor symptoms in patients with Parkinson's disease and Parkinsonian syndromes. The primary outcome measure will be the change in the MDS-UPDRS Part III score from baseline to post-stimulation. This study is expected to provide direct evidence supporting the clinical application and target selection strategies of noninvasive deep brain stimulation for the treatment of Parkinson's disease and Parkinsonian syndromes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
100
Participants with PD or PDS receive TIS. Each session lasts 30 minutes for 3 consecutive days. The study uses a crossover design with AB sequence (Active → Sham). Active stimulation: current 1.5-4 mA (patient's maximum tolerated), carrier frequency 2000 Hz, frequency offset 130 Hz; Sham stimulation: current 1.5-4 mA, carrier frequency 2000 Hz, frequency offset 0 Hz.
Participants with PD or PDS receive TIS. Each session lasts 30 minutes for 3 consecutive days. The study uses a crossover design with BA sequence (Sham → Active). Sham stimulation: current 1.5-4 mA, carrier frequency 2000 Hz, frequency offset 0 Hz. Active stimulation: current 1.5-4 mA (patient's maximum tolerated), carrier frequency 2000 Hz, frequency offset 130 Hz;
Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital
Shanghai, China
Efficacy of temporal interference stimulation (TIS) on motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The MDS-UPDRS Part III is a rater-administered motor examination used to evaluate the severity of motor impairment in patients with idiopathic Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 132, with lower scores indicating less severe motor symptoms. Changes from baseline after real or sham stimulation will be analyzed and compared between groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Secondary motor outcome
The UMSARS is a rater-administered scale used to assess disease severity in patients with Parkinsonian syndromes, particularly multiple system atrophy. The total score ranges from 0 to 104, with a higher score indicating greater disease severity. The change in UMSARS score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Secondary motor outcome
The Freezing of Gait Questionnaire is used to assess the severity and frequency of freezing of gait in patients with idiopathic Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 24, with a higher score indicating more severe freezing of gait. The change in FOGQ score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Secondary motor outcome
The Berg Balance Scale is a rater-administered scale used to assess balance function and fall risk. The total score ranges from 0 to 56, with a higher score indicating better balance function. The change in Berg Balance Scale score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Hamilton Anxiety Rating Scale-14（HAMA-14）is a rater-administered scale used to assess the severity of anxiety symptoms. The total score ranges from 0 to 56, with a higher score indicating more severe anxiety. The change in HAMA-14 score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Hamilton Depression Rating Scale-17（HAMD-17）is a rater-administered scale used to assess the severity of depressive symptoms. The total score ranges from 0 to 52, with a higher score indicating more severe depression. The change in HAMD-17 score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Mini-Mental State Examination（MMSE）is a brief cognitive screening scale used to assess global cognitive function. The total score ranges from 0 to 30, with a higher score indicating better cognitive function. The change in MMSE score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Montreal Cognitive Assessment（MoCA）is a brief cognitive screening scale used to assess global cognitive function, particularly mild cognitive impairment. The total score ranges from 0 to 30, with a higher score indicating better cognitive function. The change in MoCA score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Non-Motor Symptoms Scale（NMSS）is a rater-administered scale used to assess the severity and frequency of non-motor symptoms in patients with Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 360, with a higher score indicating a greater non-motor symptom burden. The change in NMSS score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on non-motor symptoms in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction（SCOPA-AUT）is a patient-reported scale used to assess autonomic symptoms in patients with Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 69, with a higher score indicating more severe autonomic dysfunction. The change in SCOPA-AUT score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on quality of life in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The Parkinson's Disease Questionnaire-39 Summary Index（PDQ-39 SI）is a patient-reported scale used to assess health-related quality of life in patients with Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 100, with a higher score indicating poorer quality of life. The change in PDQ-39 SI score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on quality of life in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The MDS-UPDRS Part I is used to assess non-motor experiences of daily living in patients with idiopathic Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 52, with a higher score indicating more severe non-motor symptom burden. The change in MDS-UPDRS Part I score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Efficacy of TIS on quality of life in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
The MDS-UPDRS Part II is used to assess motor experiences of daily living in patients with idiopathic Parkinson's disease and Parkinsonian syndromes. The total score ranges from 0 to 52, with a higher score indicating greater motor-related impairment in daily living. The change in MDS-UPDRS Part II score from baseline to after stimulation will be compared between the real and sham stimulation groups.
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Potential mechanisms underlying the therapeutic effects of TIS in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
Changes in resting-state EEG β-band oscillation power before and after stimulation
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Potential mechanisms underlying the therapeutic effects of TIS in patients with idiopathic Parkinson's disease and Parkinsonian syndromes
Changes in whole-brain resting-state fMRI functional connectivity strength, with exploratory analyses focusing on the sensorimotor and basal ganglia networks, before and after stimulation
Time frame: Baseline, 3 days after sham stimulation, and 3 days after active stimulation.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
The number and severity of all AEs and SAEs will be collected and monitored throughout the study to evaluate the safety and tolerability of the intervention.
Time frame: From baseline through study completion (up to 3 weeks)
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