Transcutaneous Magnetic Spinal Cord Stimulation for Freezing of Gait in Parkinson's Disease

Study Overview
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Brief Summary
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Dopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait, balance problems and other gait issues directly impacts patients' quality of life. Experimental epidural spinal cord stimulation studies have suggested positive effects on locomotion among PD patients, but the effects of non invasive stimulation have never been explored.

Detailed Description
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The present study is a randomized, double-blind, placebo-controlled, parallel, phase II clinical trial that will assess the efficacy and safety of transcutaneous magnetic spinal cord stimulation in PD patients who have gait and balance changes refractory to dopaminergic therapy.

Official Title
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Transcutaneous Magnetic Spinal Cord Stimulation for Freezing of Gait in Parkinson's Disease

Conditions
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Gait Disorders, Neurologic

Intervention / Treatment
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* Device: Non-invasive magnetic stimulation of the spinal cord
* Other: Coil will not be connected to the stimulation device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (not pregnant) aged between 21 and 80 years old; Participants with idiopathic Parkinson's disease in Hoehn Yahr stages between 2 and 4 (moderate disease) during off-medication, whose primary symptom includes change in gait and / or balance (score equal to or greater than 1 in subitem 2.12 of the MSD scale -UPDRS [gait and balance]). The participant must also present freezing (block) of gait (score equal to or greater than 1 in sub-item 2.13 of the MSD-UPDRS scale - freezing). Patients should experience the above symptoms even though they are optimized from the medication point of view. The criteria for being optimized will be defined by a neurologist specialized in movement disorders who will evaluate the case. The presence of freezing will be confirmed through a specific scale (FOG score). Mini-examination of mental status greater than or equal to 24 points; Able to give informed consent in accordance with institutional policies; Able to meet all testing and monitoring requirements, as defined by the study protocol; Exclusion Criteria: Patients with unstabilized psychiatric comorbidities Impossibility to consent to your participation in the study. Patients with uncontrolled infection or other pre-existing uncontrolled medical conditions (eg, decompensated diabetes, high blood pressure, pneumo or symptomatic heart disease). Concomitant treatment with other experimental drugs. Pregnant or breastfeeding women. Presence of chronic pain in the lower limbs. Patients who are unable to walk without assistance (cane, crutch, walker) or help from another person when they are without their medications for Parkinson's disease (off-medication).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 81 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
Interventional Model Description: Study is a randomized, double-blind, placebo-controlled, parallel, phase II clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACTIVE<br>In the active group, non-invasive transcutaneous magnetic stimulation of the dorsal spine will be applied by placing a circular magnetic coil (Magventure®️ MagPro®️ R20) on the skin, in the upper thoracic region (chest level T2-T3). The stimulation intensity will represent 100% of the motor threshold, this determined by abdominal muscle contractions, found from single pulses, applied gradually every 10 seconds until the contractions appear. The intermittent theta burst stimulation protocol will consist of 20 stimulation trains, with an interval of 8 seconds between trains, each train will have 20 bursts, and each burst will have 3 pulses at 50 Hz repeated at 5 Hz. In total, 1200 pulses will be applied for 3 minutes and 58 seconds. | Device: Non-invasive magnetic stimulation of the spinal cord<br>* Non-invasive transcutaneous magnetic stimulation of the dorsal spine will be applied by placing a circular magnetic coil (Magventure®️ MagPro®️ R20) on the skin, in the upper thoracic region (chest level T2-T3). The stimulation intensity will represent 100% of the motor threshold. The intermittent theta burst stimulation protocol will consist of 20 stimulation trains, with an interval of 8 seconds between trains, each train will have 20 bursts, and each burst will have 3 pulses at 50 Hz repeated at 5 Hz. In total, 1200 pulses will be applied for 3 minutes and 58 seconds<br>* Other names: TMS;|
| Placebo Comparator: PLACEBO<br>In the placebo group, a coil will be allocated in the T2-T3 thoracic region, however this coil will not be connected to the stimulation device, and another active coil will be positioned about 15cm behind, far from its field of view, to provide idea from the sound stimulus that is being stimulated. To create a sensation of muscle contraction and impression of active stimulation, both the placebo and active groups will be subjected to the sensory effect of transcutaneous electrical neurostimulation (TENS). | Other: Coil will not be connected to the stimulation device<br>* coil will not be connected to the stimulation device, and another active coil will be positioned about 15cm behind, far from its field of view, to provide idea from the sound stimulus that is being stimulated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TUG | The primary outcome will be the change in gait speed between pre-stimulation and post-stimulation conditions between the two groups (active and placebo) assessed using the 5-meter total Timed Up and Go Test (TUG). Mixel model ANOVA, with TUG as the dependent variable, and time and group as independent variables -'group' would have two levels ('active' and 'placebo'). Our alternative hypothesis is that 'the time vs. group' interaction effect is significant. Then we should use post hoc statistical tests to explore our data further and to compare the effects of active versus placebo at different time levels. | Post-stimulation: immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcomes will be the change on other gait measures, gait speed. | Evaluate the gait speed through measurements obtained through sensors for gait, during the gait of five meters. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | 
| Secondary outcomes will be the effects of stimulation on other gait measures, step length, stride length and step width. | Evaluate step length, stride length and step width through measurements obtained through sensors for gait, during the gait of five meters. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | 
| Secondary outcomes will be the effects of stimulation on other gait measures, cadencia. | Evaluate the cadencia through measurements obtained through sensors for gait, during the gait of five meters. | Baseline, immediately after the fifth day of stimulation, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | 
| Secondary outcomes will be the effects of stimulation on balance after noninvasive magnetic stimulation of the dorsal spine in patients with parkinson's disease. | Evaluate the improvement of the balance through the application of questionnaires,which will be the Activities-specific Balance Confidence Scale (ABC) and Falls Efficacy Scale (FES I). | Baseline, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | 
| Determination of possible adverse effects of noninvasive magnetic stimulation of the dorsal spine in patients with parkinson's disease. | The patient will be actively questioned about the appearance of adverse effects of noninvasive stimulation of the dorsal cord. | Immediately after the fifth day of stimulation, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | 
| Assess the effects of transcutaneous magnetic stimulation of the dorsal cord on quality of life in patients with parkinson's disease | The questionnaire Parkinson Disease Questionnaire-39 (PDQ-39) will be applied. | Baseline, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | 
| To evaluate the effects of noninvasive stimulation of the dorsal cord in the presence of freezing gait, through the application of questionnaires. | The questionnaires New Freezing of Gait Questionnaire (NFOG-Q), Sub-items 2.12 and 2.13 MDS-UPDRS will be applied. | Baseline, immediately after the fifth day of stimulation, seven, fourteen, twenty-one and twenty-eight days after finishing the stimulation. | 
| Assess the effects of transcutaneous magnetic stimulation of the spinal cord on the other motor symptoms of Parkinson's disease. | Other motor effects will be assessed by applying the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) item III and FOG SCORE. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | 
| Assess the effects of transcutaneous magnetic stimulation of the spinal cord on cognition of Parkinson's disease. | Possible changes in cognition will be assessed based on the application of the Frontal assessment battery (FAB). | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. |