Neural Mechanism of Theta-Burst Transcranial Magnetic Stimulation (TBS) for Freezing of Gait

To investigate the treatment effect of Theta-burst Transcranial Magnetic Stimulation (TBS) on patients with freezing of gait (FOG) and the underlying neural mechanism.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Magnetic Stimulation; Freezing of Gait
• Intervention / Treatment: Device: transcranial magnetic stimulation

Detailed Description

This was a open-label clinical trial. Forty patients with FOG were treated with TBS for 5 days. Each patient was given a high-dose iTBS of 9000 pulses/day for each target to stimulate the lower extremity motor area and dorsolateral prefrontal lobe respectively. The stimulation sequence of the two targets was randomized among subjects, and the stimulation sequence within the subjects remained unchanged throughout the course of treatment for 5 consecutive days (18000 pulses/day, 90,000 pulses in total).

Before the TBS treatment, the Freezing of Gait Questionnaire, the Timed up and go test, the Standing Start 180° Turning Test, the Unified Parkinson's Disease Rating Scale, and the Non-motor Symptom Scale, the Pittsburgh sleep quality index were obtained by a trained investigator to assess baseline severity. The patients had receiving a battery measure of neuropsychological tests(mini-mental state examination, Montreal cognitive assessment, digital span test, verbal fluency test, Hamilton depression/anxiety scale) and magnetic resonance imaging (MRI) scan in multimodalities, electroencephalography (EEG) record, and biological specimens (blood, urine, etc.). In the second day after the last treatment, all the tests, MRI, EEG and biological specimens were reassessed. Patients were instructed to focus their answers on the past 5 days.

The clinical symptom and cognition of participants were followed in one month and two month after the last treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: panpan hu, Ph.D.; Phone Number: +8655162923704; Email: hpppanda9@126.com
• Study Contact Backup: Name: fengbo xing, Mr.; Phone Number: +8655162923704; Email: 1599329305@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230032
      • Recruiting
      • Cognitive Neuropsychology Lab Anhui Medical University
      • Contact: panpan hu, Ph.D.; Phone Number: +8655162923704; Email: hpppanda9@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. diagnosis of FOG with expertise in movement disorders.
2. the score of item 3 of the FOG questionnaire ≥1.
3. ongoing treatment with a stable dose of any medication for 2 months.
4. 40 years of age or older.

Exclusion Criteria:

1. a history of addiction, psychiatric disorders, or neurological diseases other than PD.
2. focal brain lesions on T1-/T2-weighted fluid-attenuated inversion recovery images.
3. anti-PD medication adjustments during rTMS treatment.
4. history of substance abuse within the past 6 months.
5. nonremovable metal objects in or around the head.
6. previously received rTMS treatment.
7. prior history of seizure or history in first-degree relatives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Real Stimulation; The continuous theta burst stimulation (iTBS) protocol lasted 10 min and consisted of 1800 pulses. In the iTBS session, this 10min protocol was repeated for ten times (18000 pulses in total) separated by 50 min breaks (controlled by a stopwatch). MRI dataset should be acquired before the first iTBS session and after the last iTBS session.	Device: transcranial magnetic stimulation; The stimulations were performed by MagStim Rapid2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Standing-Start 180° Turn Test (SS-180)	The participants walk for a distance of five meters from a sitting position and come back to the chair after turning 180° around a traffic cone in a 0.7 m × 0.7 m target box.The time during the 180° turn (SS180) are measured. The time is recorded in seconds, and the longer the time, the more severe the symptoms	changes from baseline to 1-week post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The timed up and go test (TUG)	The participants walk for a distance of five meters from a sitting position and come back to the chair after turning 180° around a traffic cone in a 0.7 m × 0.7 m target box .The time during the whole course are measured. The time is recorded in seconds, and the longer the time, the more severe the symptoms	changes from baseline to 1-week post-treatment
The Freezing of Gait Questionnaire (FOGQ)	This is an very common clinical motor estimating scale for evaluating FOG. 6 items and each item scored between 0 and 4 points (24 scores in total). A higher score indicates more severe symptoms	changes from baseline to 1-week post-treatment
Unified Parkinson's Disease Rating Scale III (UPDRSIII)	This is an very common clinical motor estimating scale, 14 items and 108' in total. Higher scores indicate worse symptoms.	changes from baseline to 1-week post-treatment
Non-motor symptoms questionnaire (NMSS)	This is a very common clinical scale with nine domains (30 items). Each item was scored on "severity" range from 1 to 3 and "frequency" range from 1 to 4. Higher scores indicate worse symptoms.	changes from baseline to 1-week post-treatment
HAMD (Hamilton Depression Scale)	This scale was compiled by Hamilton in 1960, is the most common clinical to assess Depression Scale. In this study, 17 versions were selected, and there were 17 questions. The subjects were assessed for their depression in the past week. Each question scored between 0 and 4 points.Higher scores indicate more depressive symptoms.	changes from baseline to 1-week post-treatment
HAMA (Hamilton Anxiety Scale)	This scale was compiled by Hamilton in 1959.It was one of the most commonly used scales in psychiatric clinic, including 14 items. It is often used in clinical diagnosis and degree classification of anxiety disorder. The subjects were assessed for their anxiety in the past week. Each question scored between 0 and 4 points. The higher the score, the more symptoms of anxiety.	changes from baseline to 1-week post-treatment
Mini Mental State Exam (MMSE)	The commonly used scale of cognitive function test can reflect the mental state and the degree of cognitive dysfunction of the subjects comprehensively, accurately and rapidly. A total of 30 questions, each correct answer 1 point	changes from baseline to 1-week post-treatment
Montreal Cognitive Assessment (MoCA)	The changes in MoCA will constitute assess response to rTMS the secondary research outcome measure used to.MoCA was developed by Nasreddine et al. based on clinical experience and reference to the MMSE cognitive items and scores, and the final version was finalized in November 2004. We adopted a localized version (Mandarin version#includes 2 alternative versions) in line with the Chinese cultural background.It includes 11 inspection items in 8 cognitive fields, including visual structure skills, executive function, naming, attention and calculation, language, abstract thinking, memory, and orientation. With a total score of 30 or more than 26, it is normal. Anyone who has been education for less than 12 years will need to add one point to his final score. The final score of the higher the better, and we hope the subjects' scores will improve after treatment.	changes from baseline to 1-week post-treatment

Collaborators and Investigators

• Sponsor: Anhui Medical University
• Investigators: Principal Investigator: Kai Wang, Ph.D., Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Freezing of Gait
• Other Study ID Numbers: AHMU-TMS-FOG-twotargets

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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