Trial Outcomes & Findings for rTMS for the Treatment of Freezing of Gait in Parkinson's Disease (NCT NCT03219892)

Results Overview

NFOGQ ranges from 0-24 points. It is used to quantify changes of the FOG frequency and severity. Higher scores mean a worse outcome.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

30 participants

Primary outcome timeframe

Pre-treatment, post-treatment 4 weeks

Results posted on

2021-05-14

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	20	10
Overall Study COMPLETED	20	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

rTMS for the Treatment of Freezing of Gait in Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	62.65 years STANDARD_DEVIATION 10.56 • n=5 Participants	65.60 years STANDARD_DEVIATION 8.68 • n=7 Participants	63.63 years STANDARD_DEVIATION 9.92 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment China	20 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants
New Freezing of Gait Questionnaire	15.85 units on a scale STANDARD_DEVIATION 4.87 • n=5 Participants	14.70 units on a scale STANDARD_DEVIATION 4.03 • n=7 Participants	15.34 units on a scale STANDARD_DEVIATION 4.43 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.
Changes of the New Freezing of Gait Questionnaire (NFOGQ) Score	-1.60 score on a scale Interval -2.37 to -0.83	-2.13 score on a scale Interval -2.97 to -1.29

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.
Motor Subscale of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III)	-5.79 score on a scale Interval -7.86 to -3.71	-0.24 score on a scale Interval -3.17 to 2.69

SECONDARY outcome

Timeframe: Pre-treatment, post-treatment 4 weeks

To assess the changes of straight walking function.

Outcome measures

Outcome measures
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.
Cadence	2.67 steps/minute Interval -1.27 to 6.61	-7.99 steps/minute Interval -13.68 to -2.3

SECONDARY outcome

Timeframe: Pre-treatment, post-treatment 4 weeks

To assess the changes of turning function.

Outcome measures

Outcome measures
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.
Turning Duration	-0.47 seconds Interval -0.89 to -0.05	0.59 seconds Interval -0.55 to 0.71

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	High-frequency rTMS n=20 Participants 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.	Sham rTMS n=10 Participants 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.
Changes of Brain Functional Connectivity. before treatment	0.33 correlation coefficients Standard Deviation 0.12	0.33 correlation coefficients Standard Deviation 0.18
Changes of Brain Functional Connectivity. after treatment	0.49 correlation coefficients Standard Deviation 0.19	0.50 correlation coefficients Standard Deviation 0.18

Adverse Events

High-frequency rTMS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sham rTMS

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	High-frequency rTMS n=20 participants at risk 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.	Sham rTMS n=10 participants at risk 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.
Nervous system disorders mild but tolerable headache	15.0% 3/20 • 4 weeks	10.0% 1/10 • 4 weeks

Additional Information

Piu Chan

Xuanwu Hospital

Phone: 010-83198677

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place