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The goal of this clinical trial is to learn whether a type of brain stimulation called transcranial temporal interference stimulation (TIS) of the internal globus pallidus (GPi) can help improve movement symptoms in people with Parkinson's disease. The study will also look at how TIS changes brain activity related to these improvements.
The main questions this study aims to answer are:
Researchers will compare people who receive active TIS with those who receive sham (placebo-like) stimulation to see whether active TIS leads to better movement outcomes.
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TIS Group | Experimental | Participants in this arm will receive active transcranial temporal interference stimulation targeting the internal globus pallidus over a two-week intervention period. |
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| Sham Group | Sham Comparator | Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. However, both electrode pairs delivered currents at 2000 Hz without a frequency offset, resulting in a flat interference envelope while maintaining similar scalp sensations. The sham procedure consists of 10 sessions delivered over a two-week period, without therapeutic stimulation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Temporal Interference Stimulation (TIS) | Device | Transcranial temporal interference stimulation (TIS) is a noninvasive brain stimulation technique that delivers two high-frequency alternating currents through scalp electrodes to generate a low-frequency interference field in deep brain regions. In this study, TIS targets the internal globus pallidus (GPi) to modulate neural activity in people with Parkinson's disease. Participants receive 10 stimulation sessions over two weeks. The sham TIS condition uses the same setup but applies low-frequency currents without generating an interference pattern. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III) Score | Change in motor symptoms assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III). The total score ranges from 0 to 132, with higher scores indicating more severe motor impairment (worse outcome). | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Participants With a ≥5-point Reduction From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III) Score | A responder was defined as a participant with a reduction of at least 5 points from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) total score. Scores range from 0 to 132, with higher scores indicating more severe motor impairment; therefore, a reduction in score indicates improvement. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS I) Score | Change in non-motor symptoms assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS I) (Non-Motor Experiences of Daily Living). The total score ranges from 0 to 52, with higher scores indicating more severe non-motor symptoms (worse outcome). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Home Diary Assessment of Motor States (Medication-ON Without Dyskinesia) | The motor state will be recorded by participants using a self-completed home diary during waking hours in 30-minute intervals from awakening until bedtime. For each interval, participants will record one of the following motor states: ON with good control, ON with mild dyskinesia, ON with severe dyskinesia, or OFF. Baseline assessment will be defined as the average percentage of waking time spent in ON states over three consecutive days immediately prior to the intervention. The 1-week assessment will be defined as the average percentage of waking time spent in ON states over the five intervention days of the first intervention week, and the 2-week assessment as the average over the five intervention days of the second intervention week. The outcome measure is defined as the percentage of total recorded waking time spent in ON states, calculated from the home diary data. A higher percentage of time spent in ON states indicates milder motor symptoms and better motor control. |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai University of Sport | Shanghai | Shanghai Municipality | 200438 | China |
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| ID | Title | Description |
|---|---|---|
| FG000 | TIs Group | Participants in this arm will receive active transcranial temporal interference stimulation targeting the internal globus pallidus over a two-week intervention period. |
| FG001 | Sham Stimulation Group | Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. However, both electrode pairs delivered currents at 2000 Hz without a frequency offset, resulting in a flat interference envelope while maintaining similar scalp sensations. The sham procedure consists of 10 sessions delivered over a two-week period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All randomized participants were included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | TIs Group | Participants in this arm will receive active transcranial temporal interference stimulation targeting the internal globus pallidus over a two-week intervention period. |
| BG001 | Sham Stimulation Group |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III) Score | Change in motor symptoms assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III). The total score ranges from 0 to 132, with higher scores indicating more severe motor impairment (worse outcome). | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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From enrollment through the final follow-up visit 8 weeks after completion of the 2-week intervention period, for an overall adverse-event monitoring period of approximately 10 weeks.
Adverse events were collected from enrollment through the end of follow-up. Stimulation-related side effects were assessed at each stimulation session using a standardized checklist, and other adverse events occurring during the study period were recorded through spontaneous participant reports and follow-up assessments. For this parallel-group study, the number at risk was the number of participants assigned to each group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TIs Group | Participants in this arm will receive active transcranial temporal interference stimulation targeting the internal globus pallidus over a two-week intervention period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fracture | Injury, poisoning and procedural complications | Non-systematic Assessment | Fracture requiring surgical treatment during follow-up and judged by the study physician to be unrelated to temporal interference stimulation or study procedures. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Scalp pain | General disorders | Systematic Assessment | Local scalp pain at the electrode site; non-serious. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yu Liu | Shanghai University of Sport | + 86 021 65507351 | yuliu@sus.edu.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 9, 2024 | Apr 21, 2026 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 9, 2024 | Apr 21, 2026 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-II (MDS-UPDRS II) Score | Change in motor symptoms affecting daily living assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-II (MDS-UPDRS II) (Motor Experiences of Daily Living). The total score ranges from 0 to 52, with higher scores indicating more severe motor difficulties in daily living (worse outcome). | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Epworth Sleepiness Scale Score | Change in daytime sleepiness assessed using the Epworth Sleepiness Scale . The Epworth Sleepiness Scale is a self-administered questionnaire consisting of 8 items, with total scores ranging from 0 to 24, where higher scores indicate greater daytime sleepiness (worse outcome). | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Sleep Scale-2 Score | Change in sleep disturbances assessed using the Parkinson's Disease Sleep Scale-2. The Parkinson's Disease Sleep Scale-2 is a patient-reported questionnaire consisting of 15 items, with total scores ranging from 0 to 60, where higher scores indicate more severe sleep disturbances (worse outcome). | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Gait Performance Measures | Changes in gait performance will be assessed using an instrumented gait mat during single-task and dual-task walking conditions. Spatiotemporal gait parameters, including gait speed, step length, stride length, step width, cadence, and gait variability, will be collected during standardized walking trials. Improvements in gait performance are indicated by increased gait speed, longer step and stride length, and reduced gait variability under both single-task and dual-task conditions. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Balance Performance Measures | Changes in balance performance will be assessed using a force platform during standardized standing balance tasks. Center of pressure (COP) parameters, including COP path length, sway area, and sway velocity, will be derived from force platform recordings to quantify postural stability. Improved balance performance is indicated by reduced COP displacement, smaller sway area, and lower sway velocity. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Magnetic Resonance Imaging (MRI) Measures | Changes in brain structure and/or function will be assessed using magnetic resonance imaging (MRI). MRI data will be acquired to evaluate intervention-related changes in brain regions associated with motor control. Imaging-derived measures may include structural and functional metrics obtained from standardized MRI protocols. | Baseline and immediately after the intervention |
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-bradykinesia Subscore | Change from baseline in the bradykinesia subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total bradykinesia subscore ranges from 0 to 48, with higher scores indicating more severe bradykinesia. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-rigidity Subscore | Change from baseline in the rigidity subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total rigidity subscore ranges from 0 to 20, with higher scores indicating more severe rigidity. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-axial Subscore | Change from baseline in the axial signs subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total axial signs subscore ranges from 0 to 20, with higher scores indicating more severe axial motor impairment. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-tremor Subscore | Change from baseline in the tremor subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total tremor subscore ranges from 0 to 40, with higher scores indicating more severe tremor. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Baseline, weekly averages during weeks 1 and 2 of the intervention |
| Change From Baseline in the Home Diary Assessment of Motor States (Medication-OFF) | The motor state will be recorded by participants using a self-completed home diary during waking hours in 30-minute intervals from awakening until bedtime. For each interval, participants will record one of the following motor states: ON with good control, ON with mild dyskinesia, ON with severe dyskinesia, or OFF. Baseline assessment will be defined as the average percentage of waking time spent in the Medication-OFF state over three consecutive days immediately prior to the intervention. Week 1 and Week 2 assessments will be calculated as the average percentage of waking time spent in the Medication-OFF state over the five intervention days of each intervention week. The outcome measure is defined as the percentage of total recorded waking time spent in the Medication-OFF state, calculated from the home diary data. A lower percentage of time spent in the Medication-OFF state indicates milder motor symptoms and better motor control. | Baseline, weekly averages during weeks 1 and 2 of the intervention |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index | Change in quality of life assessed using the Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 consists of 39 items across 8 domains, with total scores ranging from 0 to 100, where higher scores indicate poorer health-related quality of life (worse outcome). | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Mobility Domain Score | Change from baseline in the mobility domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer mobility-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Activities of Daily Living Domain Score | Change from baseline in the activities of daily living domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of daily living-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Emotional Well-being Domain Score | Change from baseline in the emotional well-being domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of emotional well-being-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Stigma Domain Score | Change from baseline in the stigma domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of stigma-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Social Support Domain Score | Change from baseline in the social support domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of social support-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Cognitions Domain Score | Change from baseline in the cognitions domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of cognitions-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Communication Domain Score | Change from baseline in the communication domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of communication-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Bodily Discomfort Domain Score | Change from baseline in the bodily discomfort domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of bodily discomfort-related quality of life. | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. However, both electrode pairs delivered currents at 2000 Hz without a frequency offset, resulting in a flat interference envelope while maintaining similar scalp sensations. The sham procedure consists of 10 sessions delivered over a two-week period.
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Parkinson's Disease duration | Mean | Standard Deviation | years |
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| levodopa equivalent daily dose | Mean | Standard Deviation | mg |
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Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. However, both electrode pairs delivered currents at 2000 Hz without a frequency offset, resulting in a flat interference envelope while maintaining similar scalp sensations. The sham procedure consists of 10 sessions delivered over a two-week period.
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| Other Pre-specified | Change From Baseline in the Home Diary Assessment of Motor States (Medication-ON Without Dyskinesia) | The motor state will be recorded by participants using a self-completed home diary during waking hours in 30-minute intervals from awakening until bedtime. For each interval, participants will record one of the following motor states: ON with good control, ON with mild dyskinesia, ON with severe dyskinesia, or OFF. Baseline assessment will be defined as the average percentage of waking time spent in ON states over three consecutive days immediately prior to the intervention. The 1-week assessment will be defined as the average percentage of waking time spent in ON states over the five intervention days of the first intervention week, and the 2-week assessment as the average over the five intervention days of the second intervention week. The outcome measure is defined as the percentage of total recorded waking time spent in ON states, calculated from the home diary data. A higher percentage of time spent in ON states indicates milder motor symptoms and better motor control. | Posted | Mean | Standard Error | percentage of waking time | Baseline, weekly averages during weeks 1 and 2 of the intervention |
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| Other Pre-specified | Change From Baseline in the Home Diary Assessment of Motor States (Medication-OFF) | The motor state will be recorded by participants using a self-completed home diary during waking hours in 30-minute intervals from awakening until bedtime. For each interval, participants will record one of the following motor states: ON with good control, ON with mild dyskinesia, ON with severe dyskinesia, or OFF. Baseline assessment will be defined as the average percentage of waking time spent in the Medication-OFF state over three consecutive days immediately prior to the intervention. Week 1 and Week 2 assessments will be calculated as the average percentage of waking time spent in the Medication-OFF state over the five intervention days of each intervention week. The outcome measure is defined as the percentage of total recorded waking time spent in the Medication-OFF state, calculated from the home diary data. A lower percentage of time spent in the Medication-OFF state indicates milder motor symptoms and better motor control. | Posted | Mean | Standard Error | percentage of waking time | Baseline, weekly averages during weeks 1 and 2 of the intervention |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index | Change in quality of life assessed using the Parkinson's Disease Questionnaire-39 (PDQ-39). The PDQ-39 consists of 39 items across 8 domains, with total scores ranging from 0 to 100, where higher scores indicate poorer health-related quality of life (worse outcome). | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS I) Score | Change in non-motor symptoms assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS I) (Non-Motor Experiences of Daily Living). The total score ranges from 0 to 52, with higher scores indicating more severe non-motor symptoms (worse outcome). | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-II (MDS-UPDRS II) Score | Change in motor symptoms affecting daily living assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-II (MDS-UPDRS II) (Motor Experiences of Daily Living). The total score ranges from 0 to 52, with higher scores indicating more severe motor difficulties in daily living (worse outcome). | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Epworth Sleepiness Scale Score | Change in daytime sleepiness assessed using the Epworth Sleepiness Scale . The Epworth Sleepiness Scale is a self-administered questionnaire consisting of 8 items, with total scores ranging from 0 to 24, where higher scores indicate greater daytime sleepiness (worse outcome). | Not Posted | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. | Participants |
| Secondary | Change From Baseline in the Parkinson's Disease Sleep Scale-2 Score | Change in sleep disturbances assessed using the Parkinson's Disease Sleep Scale-2. The Parkinson's Disease Sleep Scale-2 is a patient-reported questionnaire consisting of 15 items, with total scores ranging from 0 to 60, where higher scores indicate more severe sleep disturbances (worse outcome). | Not Posted | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. | Participants |
| Secondary | Change From Baseline in the Gait Performance Measures | Changes in gait performance will be assessed using an instrumented gait mat during single-task and dual-task walking conditions. Spatiotemporal gait parameters, including gait speed, step length, stride length, step width, cadence, and gait variability, will be collected during standardized walking trials. Improvements in gait performance are indicated by increased gait speed, longer step and stride length, and reduced gait variability under both single-task and dual-task conditions. | Not Posted | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. | Participants |
| Secondary | Change From Baseline in the Balance Performance Measures | Changes in balance performance will be assessed using a force platform during standardized standing balance tasks. Center of pressure (COP) parameters, including COP path length, sway area, and sway velocity, will be derived from force platform recordings to quantify postural stability. Improved balance performance is indicated by reduced COP displacement, smaller sway area, and lower sway velocity. | Not Posted | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. | Participants |
| Primary | Participants With a ≥5-point Reduction From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III) Score | A responder was defined as a participant with a reduction of at least 5 points from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) total score. Scores range from 0 to 132, with higher scores indicating more severe motor impairment; therefore, a reduction in score indicates improvement. | The intention-to-treat population included all randomized participants who received at least 1 stimulation session and had at least 1 post-baseline assessment for this outcome. Analyses were conducted in the ITT population using generalized estimating equations with available data and no imputation of missing outcome values. Therefore, the number analyzed in each row reflects the number of participants with observed data at that specific time point. | Posted | Count of Participants | Participants | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Magnetic Resonance Imaging (MRI) Measures | Changes in brain structure and/or function will be assessed using magnetic resonance imaging (MRI). MRI data will be acquired to evaluate intervention-related changes in brain regions associated with motor control. Imaging-derived measures may include structural and functional metrics obtained from standardized MRI protocols. | Not Posted | Baseline and immediately after the intervention | Participants |
| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Mobility Domain Score | Change from baseline in the mobility domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer mobility-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Activities of Daily Living Domain Score | Change from baseline in the activities of daily living domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of daily living-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Emotional Well-being Domain Score | Change from baseline in the emotional well-being domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of emotional well-being-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Stigma Domain Score | Change from baseline in the stigma domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of stigma-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Social Support Domain Score | Change from baseline in the social support domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of social support-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Cognitions Domain Score | Change from baseline in the cognitions domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of cognitions-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Communication Domain Score | Change from baseline in the communication domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of communication-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Other Pre-specified | Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Bodily Discomfort Domain Score | Change from baseline in the bodily discomfort domain score of the Parkinson's Disease Questionnaire-39 (PDQ-39), a disease-specific measure of health-related quality of life in Parkinson's disease. Domain scores were standardized to a scale from 0 to 100, with higher scores indicating poorer activities of bodily discomfort-related quality of life. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-bradykinesia Subscore | Change from baseline in the bradykinesia subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total bradykinesia subscore ranges from 0 to 48, with higher scores indicating more severe bradykinesia. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-rigidity Subscore | Change from baseline in the rigidity subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total rigidity subscore ranges from 0 to 20, with higher scores indicating more severe rigidity. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-axial Subscore | Change from baseline in the axial signs subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total axial signs subscore ranges from 0 to 20, with higher scores indicating more severe axial motor impairment. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| Secondary | Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III-tremor Subscore | Change from baseline in the tremor subscore of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). The total tremor subscore ranges from 0 to 40, with higher scores indicating more severe tremor. | Posted | Mean | Standard Error | scores | Baseline, immediately after 1 and 2 weeks of intervention, 2 weeks, 4 weeks, and 8 weeks after intervention. |
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| 0 |
| 19 |
| 0 |
| 19 |
| 16 |
| 19 |
| EG001 | Sham Stimulation Group | Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. However, both electrode pairs delivered currents at 2000 Hz without a frequency offset, resulting in a flat interference envelope while maintaining similar scalp sensations. The sham procedure consists of 10 sessions delivered over a two-week period. | 0 | 18 | 1 | 18 | 16 | 18 |
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| Itching | General disorders | Systematic Assessment | Scalp itching during stimulation; non-serious. |
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| Tingling | General disorders | Systematic Assessment | Scalp tingling during stimulation; non-serious. |
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| Burning | General disorders | Systematic Assessment | Scalp burning sensation during stimulation; non-serious. |
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| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment | Non-serious fall reported during follow-up and assessed by the study team as unrelated to the study intervention. |
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Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| This analysis corresponds to Week 2 average. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.013 | Mean Difference (Net) | 0.151 | 2-Sided | 95 | 0.034 | 0.268 | Intervention difference = TIs group minus sham stimulation group. Positive values indicate greater improvement in the TIs group. This analysis corresponds to Week 2 average. | Superiority |
| This analysis corresponds to Week 2 average. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.009 | Mean Difference (Net) | -0.041 | 2-Sided | 95 | -0.071 | -0.011 | Intervention difference = TIs group minus sham stimulation group. Negative values indicatea a higher improvement in the TIs group. This analysis corresponds to Week 2 average. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.350 | Mean Difference (Net) | -2.339 | 2-Sided | 95 | -7.323 | 2.644 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.655 | Mean Difference (Net) | -1.135 | 2-Sided | 95 | -6.206 | 3.936 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.370 | Mean Difference (Net) | -2.285 | 2-Sided | 95 | -7.360 | 2.789 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.040 | Mean Difference (Net) | -5.348 | 2-Sided | 95 | -10.432 | -0.264 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | 0.644 | Mean Difference (Net) | -0.778 | 2-Sided | 95 | -4.127 | 2.570 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.921 | Mean Difference (Net) | -0.172 | 2-Sided | 95 | -3.619 | 3.275 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.386 | Mean Difference (Net) | -1.507 | 2-Sided | 95 | -4.951 | 1.938 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.074 | Mean Difference (Net) | -3.137 | 2-Sided | 95 | -6.590 | 0.316 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.264 | Mean Difference (Net) | -2.066 | 2-Sided | 95 | -5.741 | 1.609 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.289 | Mean Difference (Net) | -2.005 | 2-Sided | 95 | -5.761 | 1.752 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.259 | Mean Difference (Net) | -2.131 | 2-Sided | 95 | -5.874 | 1.613 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.293 | Mean Difference (Net) | -1.987 | 2-Sided | 95 | -5.735 | 1.762 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| immediately after 2 weeks of intervention (T2) |
|
|
| 2 weeks after intervention (T3) |
|
|
| 4 weeks after intervention (T4) |
|
|
| 8 weeks after intervention (T5) |
|
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| This analysis corresponds to T2. | Generalized Estimating Equations | P value was obtained from a generalized estimating equation model adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | <0.001 | Risk Difference (RD) | 0.64 | 2-Sided | 95 | 0.40 | 0.88 | Intervention difference = TIs group minus sham stimulation group. Positive values indicatea a higher responder rate in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Generalized Estimating Equations | P value was obtained from a generalized estimating equation model adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.001 | Risk Difference (RD) | 0.50 | 2-Sided | 95 | 0.20 | 0.80 | Intervention difference = TIs group minus sham stimulation group. Positive values indicatea a higher responder rate in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Generalized Estimating Equations | P value was obtained from a generalized estimating equation model adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.002 | Risk Difference (RD) | 0.46 | 2-Sided | 95 | 0.16 | 0.75 | Intervention difference = TIs group minus sham stimulation group. Positive values indicatea a higher responder rate in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Generalized Estimating Equations | P value was obtained from a generalized estimating equation model adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.017 | Risk Difference (RD) | 0.40 | 2-Sided | 95 | 0.07 | 0.72 | Intervention difference = TIs group minus sham stimulation group. Positive values indicatea a higher responder rate in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.202 | Mean Difference (Net) | -6.005 | 2-Sided | 95 | -15.237 | 3.227 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.249 | Mean Difference (Net) | -5.585 | 2-Sided | 95 | -15.098 | 3.928 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.050 | Mean Difference (Net) | -9.486 | 2-Sided | 95 | -18.982 | 0.011 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.011 | Mean Difference (Net) | -12.414 | 2-Sided | 95 | -21.912 | -2.917 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.191 | Mean Difference (Net) | -6.151 | 2-Sided | 95 | -15.384 | 3.081 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.131 | Mean Difference (Net) | -7.331 | 2-Sided | 95 | -16.844 | 2.182 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.328 | Mean Difference (Net) | -4.728 | 2-Sided | 95 | -14.225 | 4.769 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.015 | Mean Difference (Net) | -11.754 | 2-Sided | 95 | -21.252 | -2.257 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.641 | Mean Difference (Net) | 2.194 | 2-Sided | 95 | -7.038 | 11.426 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.712 | Mean Difference (Net) | 1.791 | 2-Sided | 95 | -7.722 | 11.304 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.928 | Mean Difference (Net) | 0.435 | 2-Sided | 95 | -9.061 | 9.932 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.821 | Mean Difference (Net) | -1.094 | 2-Sided | 95 | -10.592 | 8.404 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.476 | Mean Difference (Net) | 3.352 | 2-Sided | 95 | -5.880 | 12.584 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.008 | Mean Difference (Net) | 12.910 | 2-Sided | 95 | 3.397 | 22.423 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.054 | Mean Difference (Net) | 9.330 | 2-Sided | 95 | -0.166 | 18.827 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.159 | Mean Difference (Net) | 6.819 | 2-Sided | 95 | -2.679 | 16.317 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.425 | Mean Difference (Net) | -3.751 | 2-Sided | 95 | -12.983 | 5.481 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.663 | Mean Difference (Net) | -2.108 | 2-Sided | 95 | -11.621 | 7.405 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.523 | Mean Difference (Net) | -3.092 | 2-Sided | 95 | -12.588 | 6.405 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.067 | Mean Difference (Net) | -8.876 | 2-Sided | 95 | -18.373 | 0.622 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.860 | Mean Difference (Net) | 0.830 | 2-Sided | 95 | -8.402 | 10.062 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.828 | Mean Difference (Net) | -1.049 | 2-Sided | 95 | -10.562 | 8.464 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.566 | Mean Difference (Net) | -2.778 | 2-Sided | 95 | -12.274 | 6.719 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.902 | Mean Difference (Net) | -0.595 | 2-Sided | 95 | -10.092 | 8.903 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.268 | Mean Difference (Net) | -5.213 | 2-Sided | 95 | -14.445 | 4.019 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.241 | Mean Difference (Net) | -5.681 | 2-Sided | 95 | -15.194 | 3.832 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.058 | Mean Difference (Net) | -9.195 | 2-Sided | 95 | -18.692 | 0.302 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.017 | Mean Difference (Net) | -11.563 | 2-Sided | 95 | -21.061 | -2.066 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.305 | Mean Difference (Net) | -4.823 | 2-Sided | 95 | -14.055 | 4.409 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.496 | Mean Difference (Net) | -3.300 | 2-Sided | 95 | -12.820 | 6.220 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.962 | Mean Difference (Net) | -0.230 | 2-Sided | 95 | -9.758 | 9.297 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.374 | Mean Difference (Net) | -4.359 | 2-Sided | 95 | -13.977 | 5.259 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | <0.001 | Mean Difference (Net) | -4.134 | 2-Sided | 95 | -6.003 | -2.265 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | <0.001 | Mean Difference (Net) | -3.503 | 2-Sided | 95 | -5.537 | -1.469 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | <0.001 | Mean Difference (Net) | -3.692 | 2-Sided | 95 | -5.695 | -1.690 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | <0.001 | Mean Difference (Net) | -4.347 | 2-Sided | 95 | -6.321 | -2.373 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | 0.619 | Mean Difference (Net) | -0.473 | 2-Sided | 95 | -2.342 | 1.396 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.038 | Mean Difference (Net) | -2.088 | 2-Sided | 95 | -4.061 | -0.116 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.241 | Mean Difference (Net) | -1.197 | 2-Sided | 95 | -3.199 | 0.806 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.166 | Mean Difference (Net) | -1.395 | 2-Sided | 95 | -3.369 | 0.579 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
|
| 4 weeks after intervention (T4) |
|
| 8 weeks after intervention (T5) |
|
| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.890 | Mean Difference (Net) | 0.132 | 2-Sided | 95 | -1.737 | 2.001 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.920 | Mean Difference (Net) | 0.102 | 2-Sided | 95 | -1.900 | 2.104 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.396 | Mean Difference (Net) | 0.866 | 2-Sided | 95 | -1.137 | 2.869 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.741 | Mean Difference (Net) | 0.333 | 2-Sided | 95 | -1.641 | 2.307 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |
| 2 weeks after intervention (T3) |
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| 4 weeks after intervention (T4) |
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| 8 weeks after intervention (T5) |
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| This analysis corresponds to T2. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.004 | Mean Difference (Net) | -2.774 | 2-Sided | 95 | -4.643 | -0.906 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T2. | Superiority |
| This analysis corresponds to T3. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.047 | Mean Difference (Net) | -2.028 | 2-Sided | 95 | -4.029 | -0.026 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T3. | Superiority |
| This analysis corresponds to T4. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.861 | Mean Difference (Net) | 0.178 | 2-Sided | 95 | -1.824 | 2.181 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T4. | Superiority |
| This analysis corresponds to T5. | Mixed Models Analysis | P value was obtained from a linear mixed-effects model, adjusted for sex, age, levodopa equivalent daily dose, and disease duration. | 0.248 | Mean Difference (Net) | -1.163 | 2-Sided | 95 | -3.137 | 0.810 | Intervention difference = TIs group minus sham stimulation group. Negative values indicate greater improvement in the TIs group. This analysis corresponds to T5. | Superiority |