Personalized rTMS Protocol Based on Functional Reserve to Enhance Ambulatory Function in PD Patients

Official title

Safety and Efficacy of Personalized Repetitive Transcranial Magnetic Stimulation Protocol Based on Functional Reserve to Enhance Ambulatory Function in Patients With Parkinson Disease

Overview

The objective of this study was to determine the effects of protocols of repetitive transcranial magnetic stimulation (rTMS) therapy based on the functional reserve of each patient with Parkinson's disease, compared to conventional high-frequency rTMS therapy on bilateral primary motor cortex (M1). Investigators hypothesized that the functional reserve of each patient with Parkinson's disease will be different, and therefore an appropriate simulating target for rTMS therapy is needed. In addition, this approach could be more effective compared to conventional protocols applied to patient with Parkinson's disease regardless of their severity, predicted mechanism of motor function recovery, or functional reserves.

Detailed description

rTMS treatment for patients with Parkinson's disease is traditionally based on stimulating the neural network of brain. The widely-used traditional rTMS treatment protocol involves high-frequency stimulation over the bilateral primary motor cortex (M1) to enhance motor and gait functions. However, concerns have arisen regarding the effect of rTMS on motor recovery in patients with Parkinson's disease. Although still subject to debate, a possible reason for the diverse results of rTMS applied is the uniform application protocol to individuals with varying pathologies and functional reserves, aimed at enhancing recovery.

Therefore, this study was aimed to determine the effects of protocols of rTMS therapy based on the functional reserve of each patient with Parkinson's disease.

Based on screening evaluations (Timed Up and Go Test (TUG), Timed Up and Go Dual Task-Cognitive (TUG-Cog)), investigators hypothesized that patients could be categorized into two groups: 1) priority in motor functional reserve, 2) priority in cognitive functional reserve. For each group, investigators plan to randomly assign patients to experimental and control groups to demonstrate the efficacy of different rTMS protocols based on functional reserves compared to conventional high-frequency rTMS applied to the bilateral M1.

Interventions

• Device High-Frequency, ipsilateral M1
  rTMS intervention: 20 sessions of 10-Hz rTMS at 90% resting motor threshold (RMT), 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: ipsilateral primary motor cortex of lower extremity. Total rTMS sessions: once a day, 5 days per 2 weeks, for 4 weeks, totaling 10 sessions. Additional treatment: Treadmill gait training after the intervention, as well as the routine pharmacotherapy based on the guidelines for management of patients with Parkin
• Device High-Frequency, bilateral M1
  rTMS intervention: 20 sessions of 10-Hz rTMS at 90% resting motor threshold (RMT), 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: bilateral primary motor cortex of lower extremity. Total rTMS sessions: once a day, 5 days per 2 weeks, for 4 weeks, totaling 10 sessions. Additional treatment: Treadmill gait training after the intervention, as well as the routine pharmacotherapy based on the guidelines for management of patients with Parkinso
• Device High-Frequency, Lt. DLPFC
  rTMS intervention: 20 sessions of 10-Hz rTMS at 90% resting motor threshold (RMT), 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: Lt. DLPFC Total rTMS sessions: once a day, 5 days per 2 weeks, for 4 weeks, totaling 10 sessions. Additional treatment: Treadmill gait training after the intervention, as well as the routine pharmacotherapy based on the guidelines for management of patients with Parkinson's disease.
• Device High-Frequency, bilateral M1
  rTMS intervention: 20 sessions of 10-Hz rTMS at 90% resting motor threshold (RMT), 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: bilateral primary motor cortex of lower extremity. Total rTMS sessions: once a day, 5 days per 2 weeks, for 4 weeks, totaling 10 sessions. Additional treatment: Treadmill gait training after the intervention, as well as the routine pharmacotherapy based on the guidelines for management of patients with Parkinso

Primary outcome measures

• Differences of Timed Up and Go Test (TUG) [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]

Secondary outcome measures (12)

• Differences of Timed Up and Go Test (TUG) [Time frame: From baseline T0 to During-intervention T1 (2 weeks)]
• Differences of Timed Up and Go Test (TUG) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Timed Up and Go Test-Cognitive (TUG-Cog) [Time frame: From baseline T0 to During-intervention T1 (2 weeks)]
• Differences of Timed Up and Go Test-Cognitive (TUG-Cog) [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]
• Differences of Timed Up and Go Test-Cognitive (TUG-Cog) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]
• Differences of MDS-UPDRS, Part III [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of New Freezing of Gait Questionnaire (FoG-Q) [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]
• Differences of New Freezing of Gait Questionnaire (FoG-Q) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Digit span Test [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]
• Differences of Digit span Test [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Trail making Test [Time frame: From baseline T0 to Post-intervention T2 (4 weeks)]

Eligibility criteria

Inclusion criteria

• patients with Parkinson's disease, diagnosed by the United Kingdom (UK) Parkinson's Disease Society Brain Bank Diagnostic Criteria,
• Modified Hoehn and Yahr (H\&Y) scale, stage 2\~4,
• patients who can walk on flat surfaces without the need for a gait aid,
• aged ≥50 years old,
• patients willing to sign the informed consent.

Exclusion criteria

• those with contraindications to rTMS, such as epilepsy, implanted metal objects in the head, or a history of craniotomy,
• those with cognitive impairment, confirmed through the Montreal Cognitive Assessment (MoCA) test as follows: < 7 points: Illiterate < 13 points: Education duration 0.5-3 years < 16 points: Education duration 4-6 years < 19 points: Education duration 7-9 years < 20 points: Education duration 10 years or more
• those with coexisting neurological conditions, such as spinal cord injury or Stroke,
• those with major psychiatric disorders, such as major depression, schizophrenia, or dementia,
• those with severe on-off phenomena or severe dyskinesia, deemed by the investigators to render participation in the study inappropriate.
• those having contraindications to conduct an MRI study,
• those who are pregnant or lactating,
• patients who have refused to participate in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

Publications

• Yun SJ, Lee HS, Kim DH, Im S, Yoo YJ, Kim NY, Lee J, Kim D, Park HY, Yoon MJ, Kim YS, Chang WH, Seo HG. Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson's disease: study protocol for a randomized controlled trial. Trials. 2024 Aug 16;25(1):543. doi: 10.1186/s13063-024-08385-2. PMID 39152467

Identifiers

NCT: NCT06350617 · 2023-12-028

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗