Multiple System Atrophy, Parkinson's Disease, Progressive Supranuclear Palsy
Conditions
Keywords
parkinsonian disorders, transcranial magnetic stimulation, somato-cognitive action network
Brief summary
This clinical trial aims to evaluate whether individualized targeted repetitive transcranial magnetic stimulation (rTMS) can improve motor and non-motor symptoms in patients with parkinsonian disorders. The main question it aims to answer is: * Does individualized targeted rTMS alleviate symptoms of parkinsonian disorders? * Which clinical manifestations of parkinsonian syndromes are responsive to individualized targeted rTMS, and to what degree? Procedures: * Preparation (Screening) Participants will undergo clinical assessments, MRI, and EEG before the treatment. * Treatment (2 Weeks) Participants will receive a 10-day TMS treatment (once daily, Monday-Friday). Each treatment day takes approximately 3-4 hours. Participants need to keep stable medications and rehabilitation routines during this time. * Follow-up (10 Weeks) Participants will undergo follow-up assessments at the end of treatment and 10 weeks after treatment. Assessments include clinical scales, MRI, and EEG.
Detailed description
Parkinsonian disorders, including Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy, are characterized by heterogeneous motor and non-motor manifestations that may respond incompletely to conventional pharmacological and rehabilitative treatments. Repetitive transcranial magnetic stimulation may provide a noninvasive approach to modulating dysfunctional brain networks. This study aims to evaluate the feasibility, safety, and potential clinical effects of individualized, network-guided repetitive transcranial magnetic stimulation in patients with parkinsonian disorders. This is an ongoing, single-center, single-group, open-label interventional study comprising disease-specific cohorts of participants with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Individualized stimulation targets are identified using structural and functional magnetic resonance imaging, with particular attention to sites within the somato-cognitive action network. Participants receive intermittent theta burst stimulation according to the stimulation protocol specified in the intervention section of this record. Clinical, neuroimaging, and neurophysiological assessments are performed before treatment, immediately after completion of treatment, and at the prespecified follow-up visit. Clinical assessments evaluate motor function, mobility, balance, ataxia, non-motor symptoms, autonomic symptoms, orthostatic blood pressure regulation, and urinary function, as applicable to each disease cohort. Magnetic resonance imaging and electroencephalography are used to explore treatment-related changes in brain network function. Medications and rehabilitation regimens are maintained as stable as clinically feasible during the treatment period. An initial cohort of eight participants with multiple system atrophy was evaluated as an early, disease-specific pilot and exploratory analysis of the ongoing parent study. This analysis was conducted to assess treatment feasibility, safety, and preliminary clinical changes in the multiple system atrophy cohort. These participants form part of the overall study population and do not constitute a separate clinical trial. Recruitment and follow-up of the parent study are ongoing.
Interventions
DEVICETMS
Intermittent theta burst stimulation (iTBS) will be delivered using a figure-of-eight coil targeting the individualized somato-cognitive action network sites (involving superior and central region) in the left hemisphere. Stimulation intensity will be set at 100% of the resting motor threshold. The iTBS protocol will consist of bursts of 3 pulses at 50 Hz, repeated at 5 Hz. Each stimulation train include 10 bursts, with an inter-train interval of 8 seconds. A total of 60 trains will be delivered, resulting in 1800 pulses per session, with four consecutive sessions and a 50-minute interval between sessions, yielding 7200 pulses per target, and a total of 14,400 pulses per day, over ten consecutive working days.
Sponsors
Peking University First Hospital
Changping Laboratory
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnostic Criteria Clinically established or clinically probable Parkinson's Disease (PD) according to the 2015 International Parkinson and Movement Disorder Society (MDS) diagnostic criteria; Clinically established or clinically probable Multiple System Atrophy (MSA) according to the 2022 MDS diagnostic criteria; Clinically probable or clinically possible Progressive Supranuclear Palsy (PSP) according to the 2017 MDS diagnostic criteria. 2. Demographics Aged 30 to 80 years, inclusive; no gender restrictions. 3. Disease Severity and Staging PD: Modified Hoehn and Yahr (H-Y) stage 2-4; MSA: Unified Multiple System Atrophy Rating Scale (UMSARS) Part IV stage 1-4; PSP: Modified Rankin Scale (mRS) grade 2-4. 4. Informed Consent and Compliance Ability to understand and comply with the study requirements and provide written informed consent.
Exclusion criteria
1. Contraindications to TMS Presence of intracranial metallic implants or other foreign bodies, including but not limited to cochlear implants, cardiac pacemakers, or internal metallic/magnetic fragments. 2. Contraindications to EEG and MRI EEG: Known allergy to conductive paste or other EEG-related contraindications. MRI: History of claustrophobia, presence of MRI-incompatible implants, or extensive tattoos. 3. Concurrent Physical Therapies Currently receiving Transcranial Magnetic Stimulation (TMS) or other therapeutic physical modalities, such as Transcranial Direct Current Stimulation (tDCS). 4. Unstable Medical Conditions Presence of unstable systemic diseases requiring urgent pharmacological or surgical intervention. 5. Neurological and Psychiatric History Personal or family history of epilepsy; History of moderate-to-severe psychiatric or psychological disorders; Chronic insomnia or regular use of sedative-hypnotics; Current use of medications that significantly alter central nervous system excitability.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in motor symptoms measured by MDS-UPDRS Part III | Baseline to post-treatment and 10 weeks after treatment | Motor symptoms will be assessed using the Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. The total score ranges from 0 to 132, with higher scores indicating more severe motor impairment and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in mobility measured by the 5-meter Timed Up and Go test | Baseline to post-treatment and 10 weeks after treatment | Mobility will be assessed using the 5-meter Timed Up and Go test. The result is recorded as the time in seconds required to stand up from a chair, walk 5 meters, turn around, walk back, and sit down. The theoretical minimum value is 0 seconds, and there is no fixed maximum value. A longer time indicates poorer mobility and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in non-motor symptoms measured by the Non-Motor Symptoms Questionnaire | Baseline to post-treatment and 10 weeks after treatment | Non-motor symptoms will be assessed using the Non-Motor Symptoms Questionnaire. The total score ranges from 0 to 30, with higher scores indicating a greater burden of non-motor symptoms and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in motor symptoms measured by UMSARS Part II | Baseline to post-treatment and 10 weeks after treatment | Motor impairment in patients with multiple system atrophy will be assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS) Part II. The total score ranges from 0 to 56, with higher scores indicating more severe motor impairment and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in disease severity measured by PSPRS | Baseline to post-treatment and 10 weeks after treatment | Disease severity in patients with progressive supranuclear palsy will be assessed using the Progressive Supranuclear Palsy Rating Scale (PSPRS). The total score ranges from 0 to 100, with higher scores indicating greater disease severity and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in balance measured by the Berg Balance Scale | Baseline to post-treatment and 10 weeks after treatment | Balance function will be assessed using the Berg Balance Scale. The total score ranges from 0 to 56, with higher scores indicating better balance performance and a better outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in ataxia severity measured by SARA | Baseline to post-treatment and 10 weeks after treatment | Ataxia severity will be assessed using the Scale for the Assessment and Rating of Ataxia (SARA). The total score ranges from 0 to 40, with higher scores indicating more severe ataxia and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in autonomic symptoms measured by the COMPASS-31 | Baseline to post-treatment and 10 weeks after treatment | Autonomic symptoms will be assessed using the Composite Autonomic Symptom Score 31 (COMPASS-31). The total weighted score ranges from 0 to 100, with higher scores indicating more severe autonomic symptoms and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in maximal systolic blood pressure drop during active standing | Baseline to post-treatment and 10 weeks after treatment | Orthostatic blood pressure regulation will be assessed using the maximal drop in systolic blood pressure during the active standing test. The value is measured in mmHg. There is no fixed maximum value; larger systolic blood pressure drops indicate more severe orthostatic blood pressure dysregulation and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
| Change in post-void residual volume | Baseline to post-treatment and 10 weeks after treatment | Urinary dysfunction will be assessed using post-void residual volume. The value is measured in milliliters. The minimum value is 0 mL, and there is no fixed maximum value. Higher post-void residual volume indicates greater urinary retention and a worse outcome. Change from baseline will be calculated at the specified follow-up visit. |
Countries
China
Contacts
CONTACTLuhua Wei, M.D.
CONTACTKai Li, M.D.
PRINCIPAL_INVESTIGATORZhaoxia Wang, M.D.
Peking University First Hospital
Outcome results
None listed