Back to resultsThe Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD
Primary Purpose
Parkinson Disease
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
magnetic stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring freezing of gait, rTMS
Eligibility Criteria
Inclusion Criteria: Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist. Item 3 of the Freezing of Gait Questionnaire(FOG-Q) scored ≥1. Age between 40 and 80 years old. Mini-Mental State Examination score >24. Ability to walk 30 meters independently. Stable medication. Patients experienced FOG during an interview. Exclusion Criteria: Other neurological or psychiatric disorders. Severe personality disorder. History of epilepsy, seizures, or convulsions. History of head injury or stroke. Metal remains of the skull or inside the brain (outside the oral cavity). Surgeries including metallic implants or known history of metal particles in the eye, pacemakers,hearing devices transplantation, or medical pumps. Severe dyskinesia, tremor, cognitive, visual or auditory impairment. Patients who could not complete the follow-up.
Sites / Locations
- the First Affiliated Hospital of Nanjing Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Sham Comparator
Arm Label
double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA
single-site high frequency rTMS over the bilateral primary motor cortex of the lower leg
sham magnetic stimulation on motor cortex
Arm Description
Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA.
Patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral M1 of the lower leg.
Patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on M1.
Outcomes
Primary Outcome Measures
Changes of Freezing of Gait Questionnaire
The Freezing of Gait questionnaire will be used to quantify the frequency and severity of this symptom. The score will be compared to the baseline. The minimum and maximum values of the FOG-Q are 0 and 24. A higher FOG-Q score means a worse outcome. The differences in FOG-Q scores before and after treatment can be used to evaluate the effect of TMS treatment.
Secondary Outcome Measures
Changes of MDS-UPDRS
The measure mainly reflects the overall severity of Parkinson's disease motor symptoms and non-motor symptoms. A higher score means a worse outcome. The score will be compared to the baseline. The differences in MDS-UPDRS scores before and after treatment can be used to evaluate the effect of TMS treatment.
Gait speed
Gait speed (m/s) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in gait speed before and after treatment can be used to evaluate the effect of TMS treatment.
Stride length
Stride length (cm) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in stride length before and after treatment can be used to evaluate the effect of TMS treatment.
Stride time variability
Stride time variability (%) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in stride time variability before and after treatment can be used to evaluate the effect of TMS treatment.
Double support
Double support (%) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in double support before and after treatment can be used to evaluate the effect of TMS treatment.
Resting motor threshold (RMT)
RMT (% TMS output intensity) is defined as the lowest intensity required to elicit MEPs of > 50 μV in at least 5 of 10 consecutive trials while the target muscle is relaxed. RMT was determined to be the nearest 1% of the maximum stimulator output. The differences in RMT before and after treatment can be used to evaluate the effect of TMS treatment.
Cortical silent period (CSP)
The CSP (ms) is measured through electromyographic signal recording (EMG) on a target muscle and refers to the period of EMG silence following the elicitation of a motor-evoked potential (MEP) through a single TMS pulse delivered over the contralateral primary motor cortex. The differences in CSP before and after treatment can be used to evaluate the effect of TMS treatment.
Short-interval intracortical inhibition (SICI)
SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 2ms, 3ms, 4ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. SICI was expressed as the percentage ratio between the test and conditioning MEP. The differences in SICI before and after treatment can be used to evaluate the effect of TMS treatment.
Intracortical facilitation (ICF)
ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 10ms, 12, 15 ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. ICF was expressed as the percentage ratio between the test and conditioning MEP. The differences in ICF before and after treatment can be used to evaluate the effect of TMS treatment.
Short-interval intracortical facilitation (SICF)
A subthreshold first stimulus (S1) intensity was set at 1 mV and a subsequent suprathreshold second stimulus (S2) intensity was set at RMT. Interstimulus intervals were 1.0 to 5.0 milliseconds with increments of 0.5 millisecond. Ten trials for each and ten single-pulse trials were given in randomized order. SICF was expressed as the percentage ratio between the S1 and S2 MEP. The differences in SICF before and after treatment can be used to evaluate the effect of TMS treatment.
Plasma indicators
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The blood plasma was collected and frozen at - 80°C for testing. Detection of changes in plasma BDNF levels. The differences in BDNF before and after treatment can be used to evaluate the effect of TMS treatment.
Changes in functional connectivity in the brain cortex
The functional connectivity in the brain cortex will be recorded by functional MRI. The differences in brain regions' functional connectivity before and after treatment can be used to evaluate the effect of TMS treatment.
Changes in cerebral blood flow in the brain cortex
The cerebral blood flow will be assessed by arterial spin labeling scanning. The differences in blood flow before and after treatment can be used to evaluate the effect of TMS treatment.
Brian structure compared among groups
Studying the brain structure among groups. The differences in brain microstructure before and after treatment can be used to evaluate the effect of TMS treatment.
Full Information
NCT ID
NCT05925296
First Posted
June 12, 2023
Last Updated
June 28, 2023
Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
National Natural Science Foundation of China
1. Study Identification
Unique Protocol Identification Number
NCT05925296
Brief Title
The Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD
Official Title
The Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in Patients With Parkinson Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
September 1, 2023 (Anticipated)
Study Completion Date
September 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
National Natural Science Foundation of China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a double-blinded randomized study examining the effectiveness of the dual-site repetitive transcranial magnetic stimulation on Freezing of Gait (FOG) in patients with Parkinson's disease. The investigators hypothesize that treatment using magnetic stimulation on double site (including M1-LL and SMA) will improve FOG and gait symptoms in patients with Parkinson's disease.
Detailed Description
Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral primary motor cortex of the lower leg and supplementary motor area, whereas patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral primary motor cortex of the lower leg. In addition, patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on motor cortex. Assessments of FOG, gait function, motor symptoms, excitability of cortex motor (using transcranial magnetic stimulation), plasma indicators and multimodal magnetic resonance were performed three times: at baseline, one day post intervention, one month post intervention, six month post intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
freezing of gait, rTMS
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA
Arm Type
Experimental
Arm Description
Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA.
Arm Title
single-site high frequency rTMS over the bilateral primary motor cortex of the lower leg
Arm Type
Active Comparator
Arm Description
Patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral M1 of the lower leg.
Arm Title
sham magnetic stimulation on motor cortex
Arm Type
Sham Comparator
Arm Description
Patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on M1.
Intervention Type
Device
Intervention Name(s)
magnetic stimulation
Intervention Description
Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral primary motor cortex of the lower leg and supplementary motor area, whereas patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral primary motor cortex of the lower leg. In addition, patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on motor cortex.
Primary Outcome Measure Information:
Title
Changes of Freezing of Gait Questionnaire
Description
The Freezing of Gait questionnaire will be used to quantify the frequency and severity of this symptom. The score will be compared to the baseline. The minimum and maximum values of the FOG-Q are 0 and 24. A higher FOG-Q score means a worse outcome. The differences in FOG-Q scores before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six months post intervention
Secondary Outcome Measure Information:
Title
Changes of MDS-UPDRS
Description
The measure mainly reflects the overall severity of Parkinson's disease motor symptoms and non-motor symptoms. A higher score means a worse outcome. The score will be compared to the baseline. The differences in MDS-UPDRS scores before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six months post intervention
Title
Gait speed
Description
Gait speed (m/s) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in gait speed before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Title
Stride length
Description
Stride length (cm) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in stride length before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Title
Stride time variability
Description
Stride time variability (%) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in stride time variability before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Title
Double support
Description
Double support (%) was evaluated at baseline, one day post intervention, one month post intervention, six month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in double support before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Title
Resting motor threshold (RMT)
Description
RMT (% TMS output intensity) is defined as the lowest intensity required to elicit MEPs of > 50 μV in at least 5 of 10 consecutive trials while the target muscle is relaxed. RMT was determined to be the nearest 1% of the maximum stimulator output. The differences in RMT before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Cortical silent period (CSP)
Description
The CSP (ms) is measured through electromyographic signal recording (EMG) on a target muscle and refers to the period of EMG silence following the elicitation of a motor-evoked potential (MEP) through a single TMS pulse delivered over the contralateral primary motor cortex. The differences in CSP before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Short-interval intracortical inhibition (SICI)
Description
SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 2ms, 3ms, 4ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. SICI was expressed as the percentage ratio between the test and conditioning MEP. The differences in SICI before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Intracortical facilitation (ICF)
Description
ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 10ms, 12, 15 ms interstimulus interval between conditioning and test stimuli. Ten trials were acquired for each interstimulus interval. ICF was expressed as the percentage ratio between the test and conditioning MEP. The differences in ICF before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Short-interval intracortical facilitation (SICF)
Description
A subthreshold first stimulus (S1) intensity was set at 1 mV and a subsequent suprathreshold second stimulus (S2) intensity was set at RMT. Interstimulus intervals were 1.0 to 5.0 milliseconds with increments of 0.5 millisecond. Ten trials for each and ten single-pulse trials were given in randomized order. SICF was expressed as the percentage ratio between the S1 and S2 MEP. The differences in SICF before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Plasma indicators
Description
5ml of the patient's elbow vein blood was collected and centrifuged after standing and stratified. The blood plasma was collected and frozen at - 80°C for testing. Detection of changes in plasma BDNF levels. The differences in BDNF before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention
Title
Changes in functional connectivity in the brain cortex
Description
The functional connectivity in the brain cortex will be recorded by functional MRI. The differences in brain regions' functional connectivity before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, six month post intervention
Title
Changes in cerebral blood flow in the brain cortex
Description
The cerebral blood flow will be assessed by arterial spin labeling scanning. The differences in blood flow before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, six month post intervention
Title
Brian structure compared among groups
Description
Studying the brain structure among groups. The differences in brain microstructure before and after treatment can be used to evaluate the effect of TMS treatment.
Time Frame
Assessed at baseline, one day post intervention, six month post intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist.
Item 3 of the Freezing of Gait Questionnaire(FOG-Q) scored ≥1.
Age between 40 and 80 years old.
Mini-Mental State Examination score >24.
Ability to walk 30 meters independently.
Stable medication.
Patients experienced FOG during an interview.
Exclusion Criteria:
Other neurological or psychiatric disorders.
Severe personality disorder. History of epilepsy, seizures, or convulsions.
History of head injury or stroke.
Metal remains of the skull or inside the brain (outside the oral cavity).
Surgeries including metallic implants or known history of metal particles in the eye, pacemakers,hearing devices transplantation, or medical pumps.
Severe dyskinesia, tremor, cognitive, visual or auditory impairment.
Patients who could not complete the follow-up.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kezhong Zhang
Phone
13770840575
Email
kezhong_zhang1969@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kezhong Zhang
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
the First Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiang Su
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kezhong Zhang
Phone
13770840575
Email
kezhong_zhang1969@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD
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