The Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD

Parkinson Disease Clinical Trial

Official title:

The Effect of Dual-site Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in Patients With Parkinson Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05925296
• Other study ID #: 2022-SRFA-020
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2022
• Est. completion date: September 1, 2023

Study information

• Verified date: June 2023
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Kezhong Zhang
• Phone: 13770840575
• Email: kezhong_zhang1969[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: September 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Idiopathic Parkinson's disease (PD), as diagnosed by a neurologist.

2. Item 3 of the Freezing of Gait Questionnaire(FOG-Q) scored =1.

3. Age between 40 and 80 years old.

4. Mini-Mental State Examination score >24.

5. Ability to walk 30 meters independently.

6. Stable medication.

7. Patients experienced FOG during an interview.

Exclusion Criteria:

1. Other neurological or psychiatric disorders.

2. Severe personality disorder. History of epilepsy, seizures, or convulsions.

3. History of head injury or stroke.

4. Metal remains of the skull or inside the brain (outside the oral cavity).

5. Surgeries including metallic implants or known history of metal particles in the eye, pacemakers,hearing devices transplantation, or medical pumps.

6. Severe dyskinesia, tremor, cognitive, visual or auditory impairment.

7. Patients who could not complete the follow-up.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• magnetic stimulation
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.

Locations

Country	Name	City	State
China	the First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiang Su

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University	National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Assessed at baseline, one day post intervention, one month post intervention, six months post intervention
Secondary	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.	Assessed at baseline, one day post intervention, one month post intervention, six months post intervention
Secondary	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.	Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention, one month post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention
Secondary	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.	Assessed at baseline, one day post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention, six month post intervention
Secondary	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.	Assessed at baseline, one day post intervention, six month post intervention