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

Parkinson's Disease and Parkinsonism Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06350617
• Other study ID #: 2023-12-028
• Status: Recruiting
• Phase: N/A
• Start date: February 20, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: Samsung Medical Center
• Contact: Won Hyuk Chang, PhD
• Phone: +82-2-3410-6068
• Email: wh.chang[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. patients with Parkinson's disease, diagnosed by the United Kingdom (UK) Parkinson's Disease Society Brain Bank Diagnostic Criteria,

2. Modified Hoehn and Yahr (H&Y) scale, stage 2~4,

3. patients who can walk on flat surfaces without the need for a gait aid,

4. aged =50 years old,

5. patients willing to sign the informed consent.

Exclusion Criteria:

1. those with contraindications to rTMS, such as epilepsy, implanted metal objects in the head, or a history of craniotomy,

2. 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

3. those with coexisting neurological conditions, such as spinal cord injury or Stroke,

4. those with major psychiatric disorders, such as major depression, schizophrenia, or dementia,

5. those with severe on-off phenomena or severe dyskinesia, deemed by the investigators to render participation in the study inappropriate.

6. those having contraindications to conduct an MRI study,

7. those who are pregnant or lactating,

8. patients who have refused to participate in this study.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease and Parkinsonism
• Parkinsonian Disorders

Intervention

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 Parkinson's disease.
• 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 Parkinson's disease.
• 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.
• 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 Parkinson's disease.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (9)

Lead Sponsor	Collaborator
Samsung Medical Center	Bucheon St. Mary's Hospital, Kumoh National Institute of Technology, Ministry of Food and Drug Safety, Korea, National Research Foundation of Korea, NEUROPHET, Saint Vincent's Hospital, Korea, Seoul National University Hospital, Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences of Timed Up and Go Test (TUG)	Measurement for gait function.	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Timed Up and Go Test (TUG)	Measurement for gait function.	From baseline T0 to During-intervention T1 (2 weeks)
Secondary	Differences of Timed Up and Go Test (TUG)	Measurement for gait function.	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Timed Up and Go Test-Cognitive (TUG-Cog)	Measurement for gait and cognitive function.	From baseline T0 to During-intervention T1 (2 weeks)
Secondary	Differences of Timed Up and Go Test-Cognitive (TUG-Cog)	Measurement for gait and cognitive function.	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Timed Up and Go Test-Cognitive (TUG-Cog)	Measurement for gait and cognitive function.	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III	Measurement for motor function of patients with Parkinson's disease. Score ranges from 0 to 132; higher score indicates more severity of disease status	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of MDS-UPDRS, Part III	Measurement for motor function of patients with Parkinson's disease. Score ranges from 0 to 132; higher score indicates more severity of disease status	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of New Freezing of Gait Questionnaire (FoG-Q)	Measurement for gait function of patients with Parkinson's disease Score ranges from 0 to 28; higher score indicates more severity of disease status	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of New Freezing of Gait Questionnaire (FoG-Q)	Measurement for gait function of patients with Parkinson's disease Score ranges from 0 to 28; higher score indicates more severity of disease status	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Digit span Test	Measurement for cognitive function	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Digit span Test	Measurement for cognitive function	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Trail making Test	Measurement for cognitive function	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Trail making Test	Measurement for cognitive function	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Gait speed)	Measurement for gait function. Gait speed (km/hr) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Gait speed)	Measurement for gait function. unit: km/hr Gait speed (km/hr) will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Stride length)	Measurement for gait function Stride length (m) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Stride length)	Measurement for gait function Stride length (m) will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Step count)	Measurement for gait function Step count will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Step count)	Measurement for gait function Step count will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Cadence)	Measurement for gait function Cadence (step count/min) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Cadence)	Measurement for gait function Cadence (step count/min) will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Swing ratio)	Measurement for gait function Swing ratio (% of swing phase of 1 gait cycle) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Swing ratio)	Measurement for gait function Swing ratio (% of swing phase of 1 gait cycle) will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Stride time)	Measurement for gait function Stride time (unit- second, time from heel strike to next heel strike) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Stride time)	Measurement for gait function Stride time (unit- second, time from heel strike to next heel strike) will be measured	From baseline T0 to Follow-up T3 (2 months)
Secondary	Differences of Gait lab parameter (Pressure distribution)	Measurement for gait function Pressure distribution (unit - pecentage, pressure distribution among heel, mild, and toe) will be measured	From baseline T0 to Post-intervention T2 (4 weeks)
Secondary	Differences of Gait lab parameter (Pressure distribution)	Measurement for gait function Pressure distribution (unit - pecentage, pressure distribution among heel, mild, and toe) will be measured	From baseline T0 to Follow-up T3 (2 months)