Efficacy of Repetitive Trans-spinal Magnetic Stimulation on Gait Freezing in PD

Study Overview
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Brief Summary
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The purpose of this randomized trial was to evaluate the efficacy of repeated sessions of trans-spinal magnetic stimulation of the spinal cord on gait abnormality, and posture abnormalities in patients with idiopathic Parkinson's disease.

Detailed Description
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Parkinson's disease is the second most common age-related neurodegenerative disease after Alzheimer's disease[1], patients with advanced Parkinson's disease (PD) often present with axial symptoms, including abnormal posture, postural instability, and gait disorder [2]. These axial symptoms are the main factors that reduce the activities of daily living (ADL) and quality of life (QOL) of PD patients. Gait disorders are among the most prevalent problems in the advanced phase of Parkinson's disease (PD) and are relatively resistant to dopaminergic treatment. Freezing of gait (FoG) affects 7% of patients in early PD and reaches 60% in advanced stages [3]. Patients with PD also suffer from pain significantly more frequently than normal subjects. Low back pain and leg pain are the most commonly experienced pain symptoms in PD patients. One of the reasons is considered to be the decreased threshold of pain due to abnormality of the dopaminergic system in the basal ganglia of PD patients [3.4]. Administration of anti-parkinsonian medication or Deep brain stimulation results in increased pain thresholds. Treatment by medication or DBS is often ineffective for low back pain caused by postural deformity and is also ineffective for radicular or peripheral neuropathic. Because pain is an important factor that reduces the ADL and QOL of patients, the establishment of new and effective therapy is essential [5.6]. A positive effect of epidural spinal cord stimulation (SCS) on locomotive activity has been reported in animal models and small cohorts of PD patients and seems to be promising.[7] Transcutaneous SCS is an emerging method that activates similar target neural structures noninvasively and has recently been explored for the treatment of spasticity after spinal cord injury.[8] Here, the investigators will assess the safety and efficacy of transcutaneous magnetic SCS on freezing of gait (FoG) and other motor symptoms in a cohort of PD patients. The investigators will be going to carry out a double-blinded randomized, case-controlled study on 38 patients who will be randomly chosen and categorize them into 2 groups, 19 patients each. The 1st group will receive real transcranial magnetic stimulation applied over each hand area High frequency 20 HZ, 80% of the motor threshold of hand, 10 sec for each train, 20 train with a total of 2000 pulses for each side plus transcutaneous spinal cord stimulation (over mid-dorsal vertebrae (thoracic 6) high frequency 10 HZ, 80% of the motor threshold of leg area10 sec for each train, 10 trains with total 1000 pulses for 10 consecutive days. The second group will receive the same protocol but the spinal stimulation will be sham stimulation as the coil lie perpendicular to the vertebral axis. Then the investigators will be going to compare the results of two groups at the end of sessions, one and two months after the last session to find out the efficacy of repetitive transcutaneous magnetic stimulation of the spinal cord on gait abnormalities and posture abnormalities, relief of pain, UPDRS, and as well as the quality of life in patients with idiopathic Parkinson's disease

Official Title
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Efficacy of Repetitive Trans-spinal Magnetic Stimulation on Gait Abnormalities in Parkinson's Disease Patients: A Double-blinded Randomized Controlled Trial

Conditions
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Adverse Effect of Drug Therapy Levodopa

Intervention / Treatment
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* Device: non invasive repetitive magnetic stimulation (real Transcranial + real trans-spinal )
* Device: non invasive repetitive magnetic stimulation (real Transcranial + sham trans-spinal )sham trans-spinal magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women of at least 40-80 years of age. Are reliable and willing to make themselves available for the duration of the study and are willing to follow up. Medically stable outpatients with a confirmed diagnosis of idiopathic PD according to United Kingdom Brain Bank Criteria Clear written informed consent from each participant in the trial. Patients after at least 6 h free of parkinsonian drugs (off-state). Exclusion Criteria: Pregnants, breastfeeding, or willing to be pregnant during the study. Presence of a clinically significant medical or psychiatric condition that may increase the risk associated with the study Participation in any other type of medical research that may interfere with the interpretation of the study. Patients with severe motor disability (bed-ridden ) that may interfere with the study procedure. History of surgical or invasive intervention for Parkinson's disease. Patients with a history of seizures or epilepsy including history in a first-degree relative or patients on treatment that reduce the seizure threshold.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: real transcranial magnetic stimulation plus real transcutaneous magnetic stimulation of spinalcord<br>the patient will receive real rTMS 2000 pulses for each hand area 20Hz 80% of Motor threshold of the hand, 10 trains, each train 10 seconds over the hand area plus 1000 pulses 10 Hz 80% of the motor threshold of the leg 10 trains, and each train 10 seconds over the mid-dorsal vertebrae for consecuative 10 days (5 days/week) | Device: non invasive repetitive magnetic stimulation (real Transcranial + real trans-spinal )<br>* repetitive transcranial magnetic stimulation and trans-spinal magnetic stimulation<br>|
| Active Comparator: real transcranial magnetic stimulation with sham transcutaneous magnetic stimulation of spinalcord<br>the patient will receive real rTMS 2000 pulses for each hand area 20Hz 80% of Motor threshold of the hand, 10 trains, each train 10 seconds plus sham stimulation 1000 pulses 10 Hz 80% of the motor threshold of the leg 10 trains, and each train 10 seconds over the mid-dorsal vertebrae for 10 consecutive days (5 sessions/week) | Device: non invasive repetitive magnetic stimulation (real Transcranial + sham trans-spinal )sham trans-spinal magnetic stimulation<br>* sham trans-spinal magnetic stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on Freezing of gait Questionnaire | Score on Freezing of gait Questionnaire | 2 months after the end of sessions | 
| Time taken for Primed up-and-go | Time taken for Primed up-and-go | 2 months after the end of sessions | 
| Time taken for 10m walk | Time taken for 10m walk | 2 months after the end of sessions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on MDS-UPDRS | Score on MDS-UPDRS | 2 months after the end of sessions | 
| Score on PDQ-39 | Score on PDQ-39 | 2 months after the end of sessions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, Parkinson's disease, therapeutic role, spinal magnetic stimulation, gait disturbance, frozen gait, UPDRS, Quality of life, Visual analogue scale