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

Not Applicable
Recruiting
Conditions
Parkinson Disease
Interventions
Device: magnetic stimulation
Registration Number
NCT05925296
Lead Sponsor
The First Affiliated Hospital with Nanjing Medical University
Brief 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.

Detailed 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 & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
53
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
double-site high frequency rTMS over the bilateral M1 of the lower leg and SMAmagnetic stimulationPatients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA.
single-site high frequency rTMS over the bilateral primary motor cortex of the lower legmagnetic stimulationPatients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral M1 of the lower leg.
sham magnetic stimulation on motor cortexmagnetic stimulationPatients in the Sham Comparator group underwent 10 sessions of double sham rTMS on M1.
Primary Outcome Measures
NameTimeMethod
Changes of Freezing of Gait QuestionnaireAssessed at baseline, one day post intervention, one month post intervention, six months post intervention

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.

Secondary Outcome Measures
NameTimeMethod
Cortical silent period (CSP)Assessed at baseline, one day post intervention

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.

Short-interval intracortical inhibition (SICI)Assessed at baseline, one day post intervention

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.

Intracortical facilitation (ICF)Assessed at baseline, one day post intervention

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.

Short-interval intracortical facilitation (SICF)Assessed at baseline, one day post intervention

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.

Plasma indicatorsAssessed at baseline, one day post intervention

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.

Changes of MDS-UPDRSAssessed at baseline, one day post intervention, one month post intervention, six months post intervention

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.

Gait speedAssessed at baseline, one day post intervention, one month post intervention, six month post intervention

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.

Stride lengthAssessed at baseline, one day post intervention, one month post intervention, six month post intervention

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.

Stride time variabilityAssessed at baseline, one day post intervention, one month post intervention, six month post intervention

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.

Double supportAssessed at baseline, one day post intervention, one month post intervention, six month post intervention

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.

Brian structure compared among groupsAssessed at baseline, one day post intervention, six month post intervention

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.

Resting motor threshold (RMT)Assessed at baseline, one day post intervention

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.

Changes in functional connectivity in the brain cortexAssessed at baseline, one day post intervention, six month post intervention

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.

Changes in cerebral blood flow in the brain cortexAssessed at baseline, one day post intervention, six month post intervention

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.

Trial Locations

Locations (1)

the First Affiliated Hospital of Nanjing Medical University

🇨🇳

Nanjing, Jiang Su, China

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