Repetitive Transcranial Magnetic Stimulation for the Treatment of Freezing of Gait in Parkinson's Disease

Repetitive Transcranial Magnetic Stimulation for the Treatment of Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial

Freezing of gait (FOG) is a common and devastating symptom in advanced stage Parkinson's disease (PD), which contributes to falls and disability. Unfortunately, there is no effective pharmacological treatment for FOG. It is suggested that the cortex-basal ganglia circuit, especially the frontal lobe, plays an important role in the pathogenesis of FOG. Repetitive transcranial magnetic stimulation (rTMS) effects over the cortex and affects the subcortical neural circuits. Previous studies have demonstrated that rTMS can improve FOG for PD patients. In the present randomized controlled trial (RCT) study, the invastigators aim to investigate the efficiency of rTMS over different motor regions of frontal lobe. The efficacy of treatment is evaluated by the score of FOG questionnaire and FOG provoking test, and the changing of neural network shown by functional magnetic resonance imaging (FMRI). Then the effects of rTMS over different brain regions will be compared for choosing a better target. The study will provide the evidence for non-invasive neuro-modulation of Parkinson's disease with freezing of gait (PD-FOG).

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease; Gait Disorders, Neurologic
• Intervention / Treatment: Device: rTMS; Device: sham stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Han Wang, doctor; Phone Number: +8618600044179; Email: 18600044179@163.com
• Study Contact Backup: Name: Dan Xu, doctor; Phone Number: +8618614069673; Email: pumc04xd@163.com

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
    • Contact: Taisheng Li, MD. PhD.; Phone Number: 86 10 65295086; Email: Litsh@263.net
    • Principal Investigator: Taisheng Li, MD, PhD
    • Sub-Investigator: Ling Luo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects fulfilled the diagnosis of idiopathic Parkinson's disease according to MDS-PD criteria
• Hoehn & Yahr (H-Y) stage was 2 or 3
• All subjects had freezing of gait which was identified by FOGQ

Exclusion Criteria:

• cognitive impairment (MMSE score<22) or major depression (HAMD-24 score>25)
• severe visual and/or haring impairment
• significant medical or psychiatric illnesses
• history of deep brain stimulation (DBS) surgery or pacemaker implantation. MRI cannot be performed in those patients
• current treatment with medication cannot be maintained during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: sham stimulation	Device: sham stimulation; the device of sham stimulation was MagStim MC-P-B70 placebo butterfly coil
EXPERIMENTAL: rTMS over M1 region; The stimulus intensity was set to 100% of the resting motor threshold. Ten sessions of rTMS were delivered over 2 weeks, one session per day for 5 consecutive days per week. Each session consisted of 10 trains of 100 pulses at 10Hz with an inter-train interval of 40 seconds. In this group, the target of rTMS is M1 region.	Device: rTMS; The device is made in London, United Kingdom
EXPERIMENTAL: rTMS over supplementary motor area (SMA); The stimulus intensity was set to 100% of the resting motor threshold. Ten sessions of rTMS were delivered over 2 weeks, one session per day for 5 consecutive days per week. Each session consisted of 10 trains of 100 pulses at 10Hz with an inter-train interval of 40 seconds. In this group, the target of rTMS is SMA region.	Device: rTMS; The device is made in London, United Kingdom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of freezing of gait questionnaire (FOGQ)	a self-assessment scale for evaluating FOG severity，the minimum value is 0, the maximum value is 24, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of freezing of gait score (FOG score)	assess the severity of FOG, the minimum value is 0, the maximum value is 36, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks
the change of score of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III	assess the motor ability, the minimum value is 0, the maximum value is 132, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks
the change of Hamilton Depression (HAMD) Scale	assess the severity of depression, the minimum value is 0, the maximum value is 76, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks
the change of Mini-mental State Examination (MMSE) scale	assess the severity of mental state, the minimum value is 0, the maximum value is 30, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks
the change of Parkinson's Disease Questionnaire (PDQ-39)	assess the quality of life, the minimum value is 0, the maximum value is 156, and higher scores mean a worse outcome.	through study completion, an average of 2 weeks
functional image of the brain (FMRI)	graph theoretical analysis of the brain network	through study completion, an average of 10 days

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 15, 2020
• Primary Completion (ANTICIPATED): April 14, 2022
• Study Completion (ANTICIPATED): June 14, 2022

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (ACTUAL): June 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: rTMS; freezing of gait; FMRI
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Nervous System Diseases; Gait Disorders, Neurologic
• Other Study ID Numbers: rTMSPDFOG-PUMCH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No