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

NCT07554833 | Not Yet Recruiting FDA Device

• 1 other identifier: SFNSC-2026-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PARKINSON DISEASE (Disorder); Parkinson s Disease

Keywords

rTMS; ExoMind; Parkinson's Disease; PD; Cognitive Function

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (26)

• 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

  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

  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

  From baseline to the 1-month follow up

• Change from baseline in the Montreal Cognitive Assessment (MoCA) score at the last treatment session

  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

  From baseline to the end of treatment at 3-month follow-up

Study Arms (1)

rTMS Treatment

ACTIVE COMPARATOR

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

Interventions

TMS DEVICE

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.

rTMS Treatment

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• San Francisco Neurology and Sleep Center: lead

Study Sites (1)

San Francisco Neurology and Sleep Center

San Francisco, California, 94108, United States

Location

Related Publications (16)

• 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.

  PMID: 38902308 BACKGROUND

• 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.

  PMID: 41817817 BACKGROUND

• 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.

  PMID: 35923424 BACKGROUND

• 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.

  PMID: 25686212 BACKGROUND

• 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.

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• 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.

  PMID: 32101639 BACKGROUND

• 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.

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• 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.

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MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Joy Shihui Meng, MD

CONTACT

415-666-2536; joymengmd@sf-neurology.com

Junyi Sun, MD, PhD

CONTACT

628-249-5656; office@sf-neurology.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Model Details: Prospective, open-label, single-arm clinical study

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)