Effects of Accelerated rTMS On Motor and Cognitive Function in Parkinson's Disease

Clinical Effects of Accelerated rTMS Targeting Motor Cortex on Motor and Cognitive Function in Parkinson's Disease: A Prospective Pilot Study

Parkinson's disease (PD) is a brain disorder that causes progressive problems with movement, such as slowness, stiffness, tremor, and difficulty walking. Many people with PD also develop problems with thinking and memory. Current medications can help control movement symptoms but often become less effective over time and may cause side effects. There is a need for additional treatment options that can address both movement and thinking difficulties in PD.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that uses magnetic pulses delivered to the scalp to stimulate specific areas of the brain. Previous research has shown that rTMS targeting the motor cortex (the part of the brain that controls movement) can improve motor symptoms in people with PD.

The purpose of this pilot study is to evaluate whether an accelerated course of rTMS targeting the motor cortex can improve movement and thinking abilities in people with mild to moderate Parkinson's disease. The study will enroll 40 participants aged 50 to 90 years at the San Francisco Neurology and Sleep Center.

Participants will receive 6 sessions of rTMS using the EXOMIND™ device, administered twice per week over approximately 3 weeks. Each session delivers high-frequency magnetic stimulation to the motor cortex on both sides of the brain. Participants will be assessed before treatment, at the last treatment session, and at 1-month and 3-month follow-up visits.

The primary outcome measure is the change in motor symptoms as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) at 1 month after treatment. Secondary outcomes include additional measures of walking and gait, domain-specific cognitive testing using the Creyos cognitive battery (assessing memory, attention, reasoning, and other thinking skills), the Montreal Cognitive Assessment (MoCA), depression symptoms (PHQ-9), and quality of life (PDQ-39).

This is a single-center, open-label study with no placebo or control group. Total participation duration is up to 139 days, including screening, treatment, and follow-up visits.

Study Overview

• Status: Not yet recruiting
• Conditions: PARKINSON DISEASE (Disorder); Parkinson s Disease
• Intervention / Treatment: Device: TMS

Detailed Description

Background and Rationale:

Parkinson's disease (PD) affects approximately 1-2% of adults over age 60 and is characterized by progressive motor symptoms including bradykinesia, rigidity, resting tremor, and postural instability. Cognitive impairment is also common, with approximately 50% of people with PD experiencing mild cognitive impairment and cumulative dementia prevalence reaching up to 80% over the disease course. Current pharmacological treatments provide symptomatic motor benefit but are limited by declining efficacy over time, motor fluctuations, dyskinesias, and other side effects. No disease-modifying therapy is currently available.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that modulates neural circuits through targeted electromagnetic stimulation. Multiple meta-analyses have demonstrated that rTMS significantly improves motor symptoms in PD, with pooled effect sizes (standardized mean difference) ranging from 0.46 to 0.64. High-frequency rTMS targeting the primary motor cortex (M1) produces the largest motor effect sizes (SMD 0.77-0.79). However, most existing studies have used conventional protocols requiring daily sessions over several weeks, which may limit accessibility and adherence. Additionally, prior studies have relied primarily on global motor assessments and have not systematically characterized the relationship between motor and cognitive changes following rTMS over extended follow-up periods.

Study Design:

This is a single-center, open-label, prospective pilot study conducted at the San Francisco Neurology and Sleep Center. The study consists of three phases: a screening phase (up to 14 days), an open-label treatment phase (approximately 21 days), and a follow-up phase (90 days). Total participation duration is up to 139 days.

Treatment Protocol:

Participants receive 6 sessions of high-frequency rTMS using the EXOMIND™ device (BTL-699-2), administered twice weekly over approximately 3 weeks. Each session delivers stimulation at 10-20 Hz frequency and 90-110% of resting motor threshold (RMT) intensity, with 3,000-6,000 total pulses per session. The target site is the primary motor cortex (M1) bilaterally, localized using the standard motor threshold determination procedure by identifying the scalp position that produces consistent contraction of the contralateral hand muscles. All sessions are conducted on-site with medical staff support.

Assessment Schedule:

Baseline assessments are completed during screening (Day -14 to Day -1) and include motor evaluations, cognitive testing, mood and quality of life questionnaires, vital signs, medical history, TMS safety screening, and calculation of Levodopa Equivalent Daily Dose (LEDD). A Creyos cognitive battery training session is administered at screening to familiarize participants with test procedures and reduce learning effects.

Post-treatment assessments are conducted at three time points: the last treatment session (approximately Day 21), 1-month follow-up (Day 51 ± 7 days), and 3-month follow-up (Day 111 ± 7 days). At each post-treatment time point, the full battery of motor, cognitive, mood, and quality of life assessments is repeated along with vital signs, adverse event assessment, and concomitant medication review.

The cognitive assessment approach uniquely combines the Montreal Cognitive Assessment (MoCA) for global cognitive screening with the Creyos cognitive battery for domain-specific evaluation across six domains: visual spatial working memory, episodic memory, deductive reasoning, mental rotation, verbal short-term memory, and attention. This multi-domain approach is designed to identify which specific cognitive functions may be most responsive to motor cortex rTMS.

Safety Monitoring:

Adverse events are monitored at each treatment session and follow-up visit using a standardized checklist of potential TMS-related adverse effects. Blood pressure and heart rate are recorded at the beginning and end of each treatment session and at all study visits.

Statistical Approach:

Repeated measures ANOVA will assess changes across time points for primary and secondary endpoints. Paired t-tests will evaluate changes between baseline and each post-treatment time point. Cohen's d effect sizes will be calculated for all endpoints. The proportion of participants achieving clinically meaningful improvement will be reported using established minimal clinically important differences (MCID) where available. Both intention-to-treat and per-protocol analyses will be conducted. Last observation carried forward (LOCF) will be used for sensitivity analyses in cases of missing data. A p-value of 0.05 will be considered statistically significant. Exploratory subgroup analyses may be conducted based on baseline motor severity, cognitive status, disease duration, age, and sex.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joy Shihui Meng, MD; Phone Number: 415-666-2536; Email: joymengmd@sf-neurology.com
• Study Contact Backup: Name: Junyi Sun, MD, PhD; Phone Number: 628-249-5656; Email: office@sf-neurology.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94108
      • San Francisco Neurology and Sleep Center
      • Contact: Junyi Sun, MD, PhD; Phone Number: 415-666-2536; Email: office@sf-neurology.com
      • Sub-Investigator: Junyi Sun, MD, PhD
      • Contact: Joy Meng, MD; Phone Number: 415-666-2536; Email: office@sf-neurology.com
      • Principal Investigator: Joy Meng, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be 50 to 90 years of age, inclusive, on the day of signing informed consent.
• Diagnosis of idiopathic Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria or UK Parkinson's Disease Society Brain Bank criteria.
• Hoehn and Yahr stage 1-3 (mild to moderate disease severity).
• MDS-UPDRS-III (Motor Examination) score ≥10 at screening.
• Stable doses of anti-parkinsonian medications (including levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine) for at least 4 weeks prior to screening, with no anticipated changes during the study period.
• Ability to provide written informed consent.
• Subject must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
• Sufficient visual and auditory acuity to complete motor and cognitive assessments.
• Availability and willingness to complete all scheduled study visits.
• Presence of a reliable study partner or caregiver who can provide information about the participant's motor, cognitive, and functional status.
• Ability to determine the motor threshold of the participant. The participant's motor threshold could be established as the minimum stimulus required to induce contraction of the contralateral hand muscles.
• Subjects willing and able to abstain from partaking in any treatments other than the study procedure for the improvement in motor or cognitive function, including non-invasive brain stimulation treatments other than the study procedure during study participation.
• Subjects willing and able to maintain their regular (pre-procedure) medication regimen, diet, and exercise routine without affecting significant change in either direction during study participation.
• Willingness to comply with study instructions and to return to the clinic for the required visits.
• Women of child-bearing potential are required to use birth control measures during the whole duration of the study.

Exclusion Criteria:

• Electronic implants in or near the head - rTMS devices are contraindicated for use in patients who have active or inactive implants in or near the head including device leads, deep brain stimulators, cochlear implants, ocular implants, and vagus nerve stimulators, implanted devices such as cardiac pacemakers, defibrillators, and neurostimulators.
• Metallic, ferromagnetic, or other magnetic-sensitive implants/objects in or near the head - rTMS devices are contraindicated for use in patients who have conductive, ferromagnetic, or other magnetic-sensitive metals implanted in their head (with some exceptions in the mouth - see Operator's Manual) or within 12 inches (30 cm) of the therapy coil. Examples include implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry, hair barrettes, and tattoos with metallic ink.
• Drug pumps within 12 inches (30 cm) of the therapy coil.
• Inability to determine the motor threshold of the participant (i.e., the minimum stimulus required to induce contraction of the contralateral hand muscles cannot be established).
• History of seizure disorder or epilepsy, except for a single remote seizure more than 5 years ago, which may be permitted at investigator discretion.
• Elevated risk of seizure due to traumatic brain injury with loss of consciousness >30 minutes within the past 12 months.
• Current use of medications known to significantly lower seizure threshold (e.g., clozapine, bupropion at doses >450 mg/day, theophylline, high-dose tricyclic antidepressants) or recent dose reduction of anticonvulsant medications or benzodiazepines within 4 weeks of screening.
• Atypical parkinsonism or Parkinson-plus syndromes (e.g., progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration).
• Hoehn and Yahr stage 4 or 5 (severe disease with significant disability).
• Severe dementia, defined as MoCA score below 10, or inability to follow simple verbal commands or complete basic motor and cognitive assessments.
• Rapidly progressive cognitive decline or suspected prion disease, autoimmune encephalitis.
• Brain tumor, intracranial hemorrhage within the past 12 months, arteriovenous malformation, or increased intracranial pressure.
• Acute stroke within the past 3 months.
• Prior deep brain stimulation (DBS) surgery or other neurosurgical procedures for Parkinson's disease.
• Has a current diagnosis of psychotic disorder, bipolar disorder, or other psychiatric condition that, in the investigator's opinion, would interfere with the subject's ability to participate in the trial.
• Has a current or recent history of serious suicidal ideation within the past 6 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening.
• History of substance or alcohol use disorder of moderate to severe severity according to DSM-5 criteria within 6 months before screening, or positive test result(s) for drugs of abuse (including opiates, cocaine, cannabinoids, methamphetamines, amphetamines) at screening.
• Has history of or current clinically significant and/or unstable medical condition that could interfere with study participation or pose safety concerns, including but not limited to: Moderate or severe hepatic impairment (Child-Pugh Score ≥7); Severe renal impairment (estimated creatinine clearance below 30 mL/min or serum creatinine >2 mg/dL); Unstable cardiac, vascular, or pulmonary disease Note: Subjects with chronic but stable, well-controlled conditions may be allowed in the study upon agreement with the investigator.
• Has uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg, despite diet, exercise, or a stable dose of antihypertensive therapy) at screening.
• Has clinically significant ECG abnormalities at screening, defined as: QTc interval (Fridericia's formula): ≥450 msec (males); ≥470 msec (females); Evidence of 2nd or 3rd degree atrioventricular block, or 1st degree atrioventricular block with PR interval >210 msec; Left bundle branch block; Features of new ischemia; Other clinically important arrhythmia
• Has a known malignancy or history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that, in the opinion of the investigator, is considered cured with minimal risk of recurrence).
• Had clinically significant acute illness within 7 days prior to study rTMS treatment.
• Had major surgery (e.g., requiring general anesthesia) within 2 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Note: Subjects with planned surgical procedures to be conducted under local anesthesia may participate.
• Is pregnant or breastfeeding while enrolled in this study or within 1 month after the last session of study rTMS treatment.
• Has received an investigational drug or used an invasive investigational medical device within 3 months before screening, or is currently enrolled in an investigational study.
• Prior treatment with rTMS within 6 months of screening.
• Subjects willing to partake in any treatments other than the study procedure for the improvement in cognitive function, including non-invasive brain stimulation treatments other than the study procedure, during study participation.
• Has psychological and/or emotional problems which would render the informed consent invalid, or limit the ability of the subject to comply with the study requirements.
• Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Active Comparator: rTMS Treatment; Participants with mild to moderate idiopathic Parkinson's disease (Hoehn and Yahr stage 1-3) receive 6 sessions of high-frequency repetitive transcranial magnetic stimulation (rTMS) using the EXOMIND™ device (BTL-699-2), administered twice weekly over approximately 3 weeks. Each session delivers bilateral stimulation to the primary motor cortex (M1) at 10-20 Hz and 90-110% of resting motor threshold, with 3,000-6,000 total pulses per session. Participants maintain their stable pre-study anti-parkinsonian medication regimen throughout the study. Motor function (MDS-UPDRS-III, Freezing of Gait Questionnaire, Timed Up and Go Test, gait speed), cognitive function (Montreal Cognitive Assessment, Creyos cognitive battery), depressive symptoms (PHQ-9), and quality of life (PDQ-39) are assessed at baseline, last treatment session, 1-month follow-up, and 3-month follow-up.

Device: TMS; The open-label treatment phase will consist of 6 sessions of rTMS using the EXOMIND™ device (BTL-699-2), administered twice a week over approximately 3 weeks. Each session will deliver high-frequency stimulation (10-20 Hz) at 90-110% of resting motor threshold (RMT), with 3,000-6,000 total pulses per session. The target site will be the primary motor cortex (M1), with bilateral stimulation. The motor cortex will be localized using the standard motor threshold determination procedure, identifying the scalp position that produces consistent contraction of the contralateral hand muscles. The procedure will be conducted at San Francisco Neurology and Sleep Center with medical staff support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) score at 1-month follow-up	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) is a clinician-rated assessment of motor function in Parkinson's disease. It evaluates 18 items across motor domains including speech, facial expression, rigidity, finger tapping, hand movements, pronation-supination, toe tapping, leg agility, arising from chair, gait, freezing of gait, postural stability, posture, body bradykinesia, postural tremor, kinetic tremor, rest tremor amplitude, and constancy of rest tremor. Each item is scored from 0 (normal) to 4 (severe), yielding a total score range of 0 to 132, with higher scores indicating greater motor impairment. Change from baseline is calculated as the 1-month follow-up score minus the baseline score, with negative values indicating improvement.	From baseline to the 1-month follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) score at the last treatment session	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) is a clinician-rated assessment of motor function in Parkinson's disease. It evaluates 18 items across motor domains including speech, facial expression, rigidity, finger tapping, hand movements, pronation-supination, toe tapping, leg agility, arising from chair, gait, freezing of gait, postural stability, posture, body bradykinesia, postural tremor, kinetic tremor, rest tremor amplitude, and constancy of rest tremor. Each item is scored from 0 (normal) to 4 (severe), yielding a total score range of 0 to 132, with higher scores indicating greater motor impairment. Change from baseline is calculated as the last treatment session score minus the baseline score, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) score at 3-month follow-up	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) is a clinician-rated assessment of motor function in Parkinson's disease. It evaluates 18 items across motor domains including speech, facial expression, rigidity, finger tapping, hand movements, pronation-supination, toe tapping, leg agility, arising from chair, gait, freezing of gait, postural stability, posture, body bradykinesia, postural tremor, kinetic tremor, rest tremor amplitude, and constancy of rest tremor. Each item is scored from 0 (normal) to 4 (severe), yielding a total score range of 0 to 132, with higher scores indicating greater motor impairment. Change from baseline is calculated as the 3-month follow-up score minus the baseline score, with negative values indicating improvement.	From baseline to the end of treatment at 3-month follow-up
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at 1-month follow-up	The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the 1-month follow-up score.	From baseline to the 1-month follow up
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at the last treatment session	The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the last treatment score.	From baseline to the end of treatment (approximately Day 21)
Change from baseline in the Montreal Cognitive Assessment (MoCA) score at the 3-month follow-up visit	The Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Total Score Range: 0 to 30. Interpretation: Higher scores indicate better cognitive function (a score of 26 or above is generally considered normal). Metric: The change is calculated by subtracting the baseline score from the 3-month follow-up score.	From baseline to the end of treatment at 3-month follow-up
Change from baseline in the Freezing of Gait Questionnaire (FOG-Q) score at the last treatment session	The Freezing of Gait Questionnaire (FOG-Q) is a patient-reported measure assessing the severity and impact of freezing of gait in Parkinson's disease. It consists of 6 items evaluating gait difficulties, including walking ability, daily impact of gait disturbances, frequency and duration of freezing episodes, and freezing during turning and gait initiation. Each item is scored from 0 (normal) to 4 (most severe), yielding a total score range of 0 to 24, with higher scores indicating more severe freezing of gait. Change from baseline is calculated as the last treatment session score minus the baseline score, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change from baseline in the Freezing of Gait Questionnaire (FOG-Q) score at 1-month follow-up	The Freezing of Gait Questionnaire (FOG-Q) is a patient-reported measure assessing the severity and impact of freezing of gait in Parkinson's disease. It consists of 6 items evaluating gait difficulties, including walking ability, daily impact of gait disturbances, frequency and duration of freezing episodes, and freezing during turning and gait initiation. Each item is scored from 0 (normal) to 4 (most severe), yielding a total score range of 0 to 24, with higher scores indicating more severe freezing of gait. Change from baseline is calculated as the 1-month follow-up score minus the baseline score, with negative values indicating improvement.	From baseline to the 1-month follow up
Change from baseline in the Freezing of Gait Questionnaire (FOG-Q) score at 3-month follow-up	The Freezing of Gait Questionnaire (FOG-Q) is a patient-reported measure assessing the severity and impact of freezing of gait in Parkinson's disease. It consists of 6 items evaluating gait difficulties, including walking ability, daily impact of gait disturbances, frequency and duration of freezing episodes, and freezing during turning and gait initiation. Each item is scored from 0 (normal) to 4 (most severe), yielding a total score range of 0 to 24, with higher scores indicating more severe freezing of gait. Change from baseline is calculated as the 3-month follow-up score minus the baseline score, with negative values indicating improvement.	From baseline to the 3-month follow-up
Change From Baseline in Timed Up and Go Test (TUG) at Last Treatment Session	The Timed Up and Go Test (TUG) is a clinical performance measure of functional mobility and dynamic balance. The test measures the time (in seconds) required for a participant to rise from a standard armchair, walk 3 meters at a comfortable and safe pace, turn around, walk back to the chair, and sit down. A longer time to complete the test indicates greater impairment in functional mobility. Change from baseline is calculated as the post-treatment time minus the baseline time, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change From Baseline in Timed Up and Go Test (TUG) at 1-Month Follow-Up	The Timed Up and Go Test (TUG) is a clinical performance measure of functional mobility and dynamic balance. The test measures the time (in seconds) required for a participant to rise from a standard armchair, walk 3 meters at a comfortable and safe pace, turn around, walk back to the chair, and sit down. A longer time to complete the test indicates greater impairment in functional mobility. Change from baseline is calculated as the 1-month follow-up time minus the baseline time, with negative values indicating improvement.	From baseline to the 1-month follow-up
Change From Baseline in Timed Up and Go Test (TUG) at 3-Month Follow-Up	The Timed Up and Go Test (TUG) is a clinical performance measure of functional mobility and dynamic balance. The test measures the time (in seconds) required for a participant to rise from a standard armchair, walk 3 meters at a comfortable and safe pace, turn around, walk back to the chair, and sit down. A longer time to complete the test indicates greater impairment in functional mobility. Change from baseline is calculated as the 3-month follow-up time minus the baseline time, with negative values indicating improvement.	From baseline to the 3-month follow-up
Change from baseline in Gait Speed as Measured by the 10-Meter Walk Test at the last treatment session	The 10-Meter Walk Test is a clinical performance measure of gait speed. Participants walk a 10-meter distance at their comfortable, self-selected pace, and the time to complete the middle portion of the walkway is recorded to minimize acceleration and deceleration effects. Gait speed is calculated in meters per second (m/s), with lower values indicating slower gait and greater functional impairment. Change from baseline is calculated as the post-treatment gait speed minus the baseline gait speed, with positive values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change from baseline in Gait Speed as Measured by the 10-Meter Walk Test at 1-month follow-up	The 10-Meter Walk Test is a clinical performance measure of gait speed. Participants walk a 10-meter distance at their comfortable, self-selected pace, and the time to complete the middle portion of the walkway is recorded to minimize acceleration and deceleration effects. Gait speed is calculated in meters per second (m/s), with lower values indicating slower gait and greater functional impairment. Change from baseline is calculated as the 1-month follow-up gait speed minus the baseline gait speed, with positive values indicating improvement.	From baseline to the 1-month follow-up
Change from baseline in Gait Speed as Measured by the 10-Meter Walk Test at 3-month follow-up	The 10-Meter Walk Test is a clinical performance measure of gait speed. Participants walk a 10-meter distance at their comfortable, self-selected pace, and the time to complete the middle portion of the walkway is recorded to minimize acceleration and deceleration effects. Gait speed is calculated in meters per second (m/s), with lower values indicating slower gait and greater functional impairment. Change from baseline is calculated as the 3-month follow-up gait speed minus the baseline gait speed, with positive values indicating improvement.	From baseline to the 3-month follow-up
Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Subscores (Tremor, Rigidity, Bradykinesia, Axial Symptoms) at Last Treatment Session	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Examination is decomposed into four cardinal motor domain subscores: tremor (items 3.15-3.18, range 0-40), rigidity (item 3.3, range 0-20), bradykinesia (items 3.4-3.8 and 3.14, range 0-44), and axial symptoms (items 3.1, 3.2, 3.9-3.13, range 0-28). Each item is scored 0 (normal) to 4 (severe). Higher scores indicate greater impairment. Change is calculated as post-treatment minus baseline, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Subscores (Tremor, Rigidity, Bradykinesia, Axial Symptoms) at 1-Month Follow-Up	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Examination is decomposed into four cardinal motor domain subscores: tremor (items 3.15-3.18, range 0-40), rigidity (item 3.3, range 0-20), bradykinesia (items 3.4-3.8 and 3.14, range 0-44), and axial symptoms (items 3.1, 3.2, 3.9-3.13, range 0-28). Each item is scored 0 (normal) to 4 (severe). Higher scores indicate greater impairment. Change is calculated as 1-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 1-month follow-up
Change From Baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Subscores (Tremor, Rigidity, Bradykinesia, Axial Symptoms) at 3-Month Follow-Up	The Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) Motor Examination is decomposed into four cardinal motor domain subscores: tremor (items 3.15-3.18, range 0-40), rigidity (item 3.3, range 0-20), bradykinesia (items 3.4-3.8 and 3.14, range 0-44), and axial symptoms (items 3.1, 3.2, 3.9-3.13, range 0-28). Each item is scored 0 (normal) to 4 (severe). Higher scores indicate greater impairment. Change is calculated as 3-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 3-month follow-up
Change from baseline in the following domain-specific cognitive measures assessed by the Creyos cognitive battery at the last treatment session	Cognitive performance will be assessed using the Creyos online platform. This measure evaluates specific cognitive domains through validated tasks. For this study, the following domains and their corresponding primary metrics are assessed: Memory (Monkey Ladders Task): Measures visuospatial working memory. Reasoning (Odd One Out Task): Measures deductive reasoning and fluid intelligence. Concentration (Feature Match Task): Measures attention and mental processing speed. Planning (Spatial Planning Task): Measures executive function and strategy. Scoring Parameters: Scale Title: Creyos Cognitive Assessment Score (Standardized Score). Minimum and Maximum Values: Scores are standardized with a mean of 100 and a standard deviation of 15. While theoretically open-ended, the effective range for clinical reporting is typically 0 to 150. Interpretation: Higher scores mean a better outcome, indicating superior cognitive performance relative to the normative database.	From baseline to the end of treatment (approximately Day 21)
Change from baseline in the following domain-specific cognitive measures assessed by the Creyos cognitive battery at the 1-month follow-up	Cognitive performance will be assessed using the Creyos online platform. This measure evaluates specific cognitive domains through validated tasks. For this study, the following domains and their corresponding primary metrics are assessed: Memory (Monkey Ladders Task): Measures visuospatial working memory. Reasoning (Odd One Out Task): Measures deductive reasoning and fluid intelligence. Concentration (Feature Match Task): Measures attention and mental processing speed. Planning (Spatial Planning Task): Measures executive function and strategy. Scoring Parameters: Scale Title: Creyos Cognitive Assessment Score (Standardized Score). Minimum and Maximum Values: Scores are standardized with a mean of 100 and a standard deviation of 15. While theoretically open-ended, the effective range for clinical reporting is typically 0 to 150. Interpretation: Higher scores mean a better outcome, indicating superior cognitive performance relative to the normative database.	From baseline to the 1-month follow-up
Change from baseline in the following domain-specific cognitive measures assessed by the Creyos cognitive battery at the 3-month follow-up	Cognitive performance will be assessed using the Creyos online platform. This measure evaluates specific cognitive domains through validated tasks. For this study, the following domains and their corresponding primary metrics are assessed: Memory (Monkey Ladders Task): Measures visuospatial working memory. Reasoning (Odd One Out Task): Measures deductive reasoning and fluid intelligence. Concentration (Feature Match Task): Measures attention and mental processing speed. Planning (Spatial Planning Task): Measures executive function and strategy. Scoring Parameters: Scale Title: Creyos Cognitive Assessment Score (Standardized Score). Minimum and Maximum Values: Scores are standardized with a mean of 100 and a standard deviation of 15. While theoretically open-ended, the effective range for clinical reporting is typically 0 to 150. Interpretation: Higher scores mean a better outcome, indicating superior cognitive performance relative to the normative database.	From baseline to the 3-month follow-up
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score at Last Treatment Session	The PHQ-9 is a 9-item self-report measure of depressive symptom severity. Each item is scored 0 (not at all) to 3 (nearly every day), yielding a total score of 0-27. Severity categories: minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Lower scores indicate fewer depressive symptoms. Change is calculated as post-treatment minus baseline, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score at 1-Month Follow-Up	The PHQ-9 is a 9-item self-report measure of depressive symptom severity. Each item is scored 0 (not at all) to 3 (nearly every day), yielding a total score of 0-27. Severity categories: minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Lower scores indicate fewer depressive symptoms. Change is calculated as 1-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 1-month follow-up
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Score at 3-Month Follow-Up	The PHQ-9 is a 9-item self-report measure of depressive symptom severity. Each item is scored 0 (not at all) to 3 (nearly every day), yielding a total score of 0-27. Severity categories: minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Lower scores indicate fewer depressive symptoms. Change is calculated as 3-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 3-month follow-up
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Score at Last Treatment Session	The PDQ-39 is a 39-item self-report questionnaire assessing health-related quality of life in Parkinson's disease across eight domains: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Each item is scored 0 (never) to 4 (always). A summary index score is calculated as a percentage (0-100), with lower scores indicating better quality of life. Change is calculated as post-treatment minus baseline, with negative values indicating improvement.	From baseline to the end of treatment (approximately Day 21)
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Score at 1-Month Follow-Up	The PDQ-39 is a 39-item self-report questionnaire assessing health-related quality of life in Parkinson's disease across eight domains: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Each item is scored 0 (never) to 4 (always). A summary index score is calculated as a percentage (0-100), with lower scores indicating better quality of life. Change is calculated as 1-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 1-month follow-up
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Score at 3-Month Follow-Up	The PDQ-39 is a 39-item self-report questionnaire assessing health-related quality of life in Parkinson's disease across eight domains: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Each item is scored 0 (never) to 4 (always). A summary index score is calculated as a percentage (0-100), with lower scores indicating better quality of life. Change is calculated as 3-month follow-up minus baseline, with negative values indicating improvement.	From baseline to the 3-month follow-up

Collaborators and Investigators

• Sponsor: San Francisco Neurology and Sleep Center

Publications and helpful links

General Publications

• Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020 Feb 11;323(6):548-560. doi: 10.1001/jama.2019.22360.
• Orgeta V, McDonald KR, Poliakoff E, Hindle JV, Clare L, Leroi I. Cognitive training interventions for dementia and mild cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev. 2020 Feb 26;2(2):CD011961. doi: 10.1002/14651858.CD011961.pub2.
• Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan;27(1):27-42. doi: 10.1111/ene.14108. Epub 2019 Nov 27.
• Zhang W, Deng B, Xie F, Zhou H, Guo JF, Jiang H, Sim A, Tang B, Wang Q. Efficacy of repetitive transcranial magnetic stimulation in Parkinson's disease: A systematic review and meta-analysis of randomised controlled trials. EClinicalMedicine. 2022 Jul 29;52:101589. doi: 10.1016/j.eclinm.2022.101589. eCollection 2022 Oct.
• Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021 May;20(5):385-397. doi: 10.1016/S1474-4422(21)00030-2.
• Zhang Q, Aldridge GM, Narayanan NS, Anderson SW, Uc EY. Approach to Cognitive Impairment in Parkinson's Disease. Neurotherapeutics. 2020 Oct;17(4):1495-1510. doi: 10.1007/s13311-020-00963-x. Epub 2020 Nov 17.
• Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E. Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2024 Apr 8;4(4):CD013856. doi: 10.1002/14651858.CD013856.pub3.
• Aarsland D, Batzu L, Halliday GM, Geurtsen GJ, Ballard C, Ray Chaudhuri K, Weintraub D. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021 Jul 1;7(1):47. doi: 10.1038/s41572-021-00280-3.
• Wang Y, Ding Y, Guo C. Assessment of noninvasive brain stimulation interventions in Parkinson's disease: a systematic review and network meta-analysis. Sci Rep. 2024 Jun 20;14(1):14219. doi: 10.1038/s41598-024-64196-0.
• Zhang X, Zheng L, Li Y, Wang H, Ma T, Lu S, Liu Z, Li Q, Bai Y, Sun L. Efficacy of rTMS and TBS on the motor symptoms in Parkinson's disease: a network meta-analysis. J Neurol. 2026 Mar 12;273(3):202. doi: 10.1007/s00415-026-13713-4.
• Chou YH, Hickey PT, Sundman M, Song AW, Chen NK. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 2015 Apr;72(4):432-40. doi: 10.1001/jamaneurol.2014.4380.
• Li R, He Y, Qin W, Zhang Z, Su J, Guan Q, Chen Y, Jin L. Effects of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Parkinson's Disease: A Meta-Analysis. Neurorehabil Neural Repair. 2022 Jul;36(7):395-404. doi: 10.1177/15459683221095034. Epub 2022 May 26.
• Oertel W, Schulz JB. Current and experimental treatments of Parkinson disease: A guide for neuroscientists. J Neurochem. 2016 Oct;139 Suppl 1:325-337. doi: 10.1111/jnc.13750. Epub 2016 Aug 30.
• Pringsheim T, Day GS, Smith DB, Rae-Grant A, Licking N, Armstrong MJ, de Bie RMA, Roze E, Miyasaki JM, Hauser RA, Espay AJ, Martello JP, Gurwell JA, Billinghurst L, Sullivan K, Fitts MS, Cothros N, Hall DA, Rafferty M, Hagerbrant L, Hastings T, O'Brien MD, Silsbee H, Gronseth G, Lang AE; Guideline Subcommittee of the AAN. Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee. Neurology. 2021 Nov 16;97(20):942-957. doi: 10.1212/WNL.0000000000012868.
• Halli-Tierney AD, Luker J, Carroll DG. Parkinson Disease. Am Fam Physician. 2020 Dec 1;102(11):679-691.
• Tanner CM, Ostrem JL. Parkinson's Disease. N Engl J Med. 2024 Aug 1;391(5):442-452. doi: 10.1056/NEJMra2401857. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Parkinson's Disease; rTMS; Cognitive Function; PD; ExoMind
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: SFNSC-2026-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes