Parkinson's Disease
Conditions
Keywords
freezing of gait, rTMS, fMRI
Brief summary
This study is a double blind comparative study examining the effectiveness of the rTMS treatment on Freezing of Gait (FOG) in patients with Parkinson's disease (PD). The investigators hypothesize that treatment with rTMS on supplemental motor area will improve gait quality and decrease the frequency of FOG in PD patients.
Detailed description
Freezing of gait (FOG) is a common and debilitating symptom in patients with Parkinson's disease (PD), characterized by sudden and brief episodes of inability to produce effective forward stepping. FOG is a major risk factor for falls, and greatly contributes to reduced mobility and quality of daily life. Treatment of FOG has been perceived as a very challenging task. Although various treatment approaches exist, including pharmacological and surgical options, evidence is inconclusive for many approaches and no clear treatment protocols are available until now. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neural modulation technique, has been closely applied as a treatment for various neurologic and psychiatric disorders. A recent meta-analysis demonstrated that rTMS could improve motor symptoms for PD patients with a moderate effect size. To date, however, only few rTMS studies have focused on its efficacy on FOG in patients with parkinsonism, and most of them targeted the primary motor cortex or dorsolateral prefrontal cortex . Even though some evidence indicates the involvement of the SMA in FOG, no report has described the SMA rTMS in PD patients with FOG. Moreover, few studies combined functional magnetic resonance imaging (fMRI) and rTMS to unravel the mechanism of its beneficial effects. To address these issues, the investigators conducted a randomized, double-blind, sham-controlled study to explore the efficiency of SMA-rTMS on FOG in PD patients.
Interventions
DEVICEHigh-frequency rTMS
It is delivered at a 5-second burst of 10Hz stimuli, repeated 20 times at every minute. Each treatment contains a total of 1000 pulses. Stimulus intensity is 90% of resting motor threshold. The SMA stimulation will be given using a coil centered at points 3-cm anterior to the leg motor area in the sagittal midline.
DEVICESham rTMS
The procedure will be same as the high-frequency rTMS except that the coil is 90° angled away.
Sponsors
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Idiopathic PD patients. * Presenting with FOG. * The mini-mental state examination questionnaire score above 24 points.
Exclusion criteria
* Other neurological or psychiatric disorders. * History of epilepsy, seizures or convulsions. * Metal implantation. * History of exposure to rTMS in the past (to minimizing risk of unblinding sham condition).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score | Pre-treatment, post-treatment 4 weeks | NFOGQ ranges from 0-24 points. It is used to quantify changes of the FOG frequency and severity. Higher scores mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) | Pre-treatment, post-treatment 4 weeks | The motor subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale evaluates the overall motor symptoms in PD, ranging from 0-112 points. Higher scores mean a worse outcome. |
| Cadence | Pre-treatment, post-treatment 4 weeks | To assess the changes of straight walking function. |
| Turning Duration | Pre-treatment, post-treatment 4 weeks | To assess the changes of turning function. |
| Changes of Brain Functional Connectivity. | Pre-treatment, post-treatment at 2 weeks | functional connectivity will be assessed using fMRI, which can help understand the neural mechanism of the rTMS treatment. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-frequency rTMS Patients randomized to this group will receive rTMS delivering over the supplementary motor area (SMA). Each treatment consists 1000 pulses (5-second burst of 10Hz rTMS, repeated 20 times at every minute ).Stimulus intensity is 90% of resting motor threshold. A figure-of-8 coil is connected to a biphasic magnetic stimulator, and the induced current is perpendicular to the midline.
High-frequency rTMS: It is delivered at a 5-second burst of 10Hz stimuli, repeated 20 times at every minute. Each treatment contains a total of 1000 pulses. Stimulus intensity is 90% of resting motor threshold. The SMA stimulation will be given using a coil centered at points 3-cm anterior to the leg motor area in the sagittal midline. | 20 |
| Sham rTMS Patients randomized to this group will receive the sham rTMS. The procedure is same as used in patients receiving experimental rTMS, except that the coil is angled 90° away.
Sham rTMS: The procedure will be same as the high-frequency rTMS except that the coil is 90° angled away. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | High-frequency rTMS | Sham rTMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 7 Participants | 24 Participants |
| Age, Continuous | 62.65 years STANDARD_DEVIATION 10.56 | 65.60 years STANDARD_DEVIATION 8.68 | 63.63 years STANDARD_DEVIATION 9.92 |
| New Freezing of Gait Questionnaire | 15.85 units on a scale STANDARD_DEVIATION 4.87 | 14.70 units on a scale STANDARD_DEVIATION 4.03 | 15.34 units on a scale STANDARD_DEVIATION 4.43 |
| Race/Ethnicity, Customized Chinese | 20 Participants | 10 Participants | 30 Participants |
| Region of Enrollment China | 20 participants | 10 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 3 / 20 | 1 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 |
Outcome results
Primary
Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score
NFOGQ ranges from 0-24 points. It is used to quantify changes of the FOG frequency and severity. Higher scores mean a worse outcome.
Time frame: Pre-treatment, post-treatment 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High-frequency rTMS | Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score | -1.60 score on a scale |
| Sham rTMS | Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score | -2.13 score on a scale |
Secondary
Cadence
To assess the changes of straight walking function.
Time frame: Pre-treatment, post-treatment 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High-frequency rTMS | Cadence | 2.67 steps/minute |
| Sham rTMS | Cadence | -7.99 steps/minute |
Secondary
Changes of Brain Functional Connectivity.
functional connectivity will be assessed using fMRI, which can help understand the neural mechanism of the rTMS treatment. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns.
Time frame: Pre-treatment, post-treatment at 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-frequency rTMS | Changes of Brain Functional Connectivity. | before treatment | 0.33 correlation coefficients | Standard Deviation 0.12 |
| High-frequency rTMS | Changes of Brain Functional Connectivity. | after treatment | 0.49 correlation coefficients | Standard Deviation 0.19 |
| Sham rTMS | Changes of Brain Functional Connectivity. | before treatment | 0.33 correlation coefficients | Standard Deviation 0.18 |
| Sham rTMS | Changes of Brain Functional Connectivity. | after treatment | 0.50 correlation coefficients | Standard Deviation 0.18 |
Secondary
Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III)
The motor subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale evaluates the overall motor symptoms in PD, ranging from 0-112 points. Higher scores mean a worse outcome.
Time frame: Pre-treatment, post-treatment 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High-frequency rTMS | Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) | -5.79 score on a scale |
| Sham rTMS | Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) | -0.24 score on a scale |
Secondary
Turning Duration
To assess the changes of turning function.
Time frame: Pre-treatment, post-treatment 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High-frequency rTMS | Turning Duration | -0.47 seconds |
| Sham rTMS | Turning Duration | 0.59 seconds |