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.
• 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.