Spinal Cord Stimulation for Gait Dysfunction in Parkinson's Disease

Study Overview
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Brief Summary
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Parkinson's disease (PD) is the second commonest neurodegenerative disorder, affecting over 145,000 people in the UK. Initially, PD patients experience slowness of movements, limb stiffness, and tremor. With progressive loss of neurons over time, many patients start to experience balance and walking problems, and falls, which are resistant to currently available treatments. Falls can lead to fractures and nursing home admission, and can significantly shorten patients' life expectancy. In this pilot study, the investigators will investigate the effects of spinal cord stimulation (SCS) on gait and balance in PD. Some open-labelled studies have shown possible beneficial effects of SCS in PD, although it is uncertain which type of PD patients will benefit most and which stimulation parameters work best. The investigators will assess the effects of SCS on posture and gait using a series of clinical, laboratory, imaging, and wearable measurements. The participants will receive a percutaneous implantation of a spinal cord stimulator to minimise the possible adverse effects related to the surgery. The SCS will start one month after surgery. The investigators will use a double-blind cross-over design. The participants will receive three different stimulation parameters, including sham stimulation, in a randomised order. The participants and the assessors will be blinded to the stimulation parameters.

Detailed Description
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The investigators aim to recruit up to 8 people with Parkinson's with significant gait dysfunction which is resistant to medical therapy to this study. All participants will receive implantation of a spinal cord stimulator at T8-10 levels. The procedure will be done percutaneously. The spinal cord stimulation will be commenced 2-4 weeks after surgery to allow time for recovery. Participants will receive 3 different stimulation parameters in randomised order as outlined below: Burst stimulation High frequency stimulation Sham stimulation Each parameter will last for up to 6 weeks. Both the patients and the researchers assessing the patients will be blinded to the settings parameters. At baseline and at the end of each stimulation settings, the participants will undergo a series of assessments (see secondary outcomes). At the end of the cross-over blinded period, the participants will be unblinded and offered to continue with the parameter that offered most symptomatic relief. The participants will then continue in this setting in an open label phase for another 10 weeks before their final assessment at 7 months.

Official Title
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Spinal Cord Stimulation to Reduce Imbalance and Falls in Parkinson's Disease

Conditions
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Parkinson Disease, Freezing of Gait

Intervention / Treatment
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* Device: Spinal Cord Stimulation - High Frequency SCS
* Device: Spinal Cord Stimulation - Burst SCS
* Device: Spinal Cord Stimulation - Sham SCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 45 ≤ X ≤ 85 PD diagnosis based on UK Parkinson's disease society brain bank criteria Significant gait dysfunction, particularly freezing of gait, which is resistant to optimal medical therapy Hoen and Yahr stage: 2-4 (in ON state) Stable dopaminergic treatment for at least two weeks before enrolment. Can provide informed consent Exclusion Criteria: Atypical or secondary parkinsonism e.g. vascular, drug-induced Major focal brain disorders (including malignancy or stroke) Recent (within 3 months)/current use of acetylcholinesterase inhibitors or antidopaminergic drugs Concomitant treatment with deep brain stimulation Neurological, vestibular, visual or orthopaedic diagnosis significantly interfering with gait Pregnant women or planning to become pregnant Significant chronic back pain Spinal anatomical abnormalities precluding SCS surgery Major cognitive or psychiatric illness Concomitant or recent (less than 4 months) enrolment in an interventional research trial.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High Frequency SCS<br>Participants will be randomly assigned to this arm for up to 6 weeks | Device: Spinal Cord Stimulation - High Frequency SCS<br>* High Frequency-SCS consists of delivering electrical stimulation at frequencies equal to or greater than 1kHz. This intervention will last up to 6 weeks.<br>|
| Active Comparator: Burst SCS<br>Participants will be randomly assigned to this arm for up to 6 weeks | Device: Spinal Cord Stimulation - Burst SCS<br>* Burst SCS consists of closely spaced, high frequency stimuli delivered to the spinal cord. This intervention will last up to 6 weeks.<br>|
| Sham Comparator: Sham SCS<br>Participants will be randomly assigned to this arm for up to 6 weeks | Device: Spinal Cord Stimulation - Sham SCS<br>* This intervention will last up to 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Incidence of Treatment-Emergent Adverse Events | Safety of a 28-week SCS Intervention will be assessed by measuring the number of participants with adverse events that are related to treatment | Day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Number of Participants with Incidence of Serious Adverse Events | Safety of a 28-week SCS Intervention will be assessed by measuring the number of participants with serious adverse events | Day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Number of Participants that complete the study | Safety of a 28-week SCS Intervention will be assessed by measuring the number of participants that complete the study | Day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Mean change from baseline to week 28 in participant scores on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 motor subsection in the OFF and ON medication state | Motor symptoms will be measured using the MDS-UPDRS part 3 motor subsection. Part III of the scale will be completed at baseline, visit 1 (1 day post-surgery), visit 2 (6 weeks post-surgery), visit 3 (12 weeks post-surgery), visit 4 (18 weeks post-surgery), visit 4 (28 weeks post-surgery). The scale consists of four parts; Part I Non-motor experiences of daily living (13 questions), Part II Motor Experiences of daily living (13), Part III Motor Examination (33) and Part IV Motor Complications (6). Each question has five responses that are linked to common clinical terms: 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Slight refers to symptoms with sufficiently low frequency/intensity to cause no impact on function; Mild refers to symptoms of frequency/intensity sufficient to cause modest impact on function; Moderate refers to symptoms sufficiently frequent/intense to impact considerably, but not prevent, function; Severe refers to symptoms that prevent function. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Change in Hoehn and Yahr Scoring Scale | Scores range: 1-5. Higher scores mean a worse outcome. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Change in New Freezing of Gait Questionnaire | The new freezing of gait questionnaire is a measure of freezing severity (total score range: 0-28) wherein higher scores represent worse freezing behaviour. The outcome measures represent the change in freezing of gait questionnaire score from pre-intervention (baseline visit) to each post-intervention time point. A larger, positive value represents a greater reduction in freezing severity and a better outcome. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Changes in 10 meter walk test (10MW) performance (sec) | Change in the duration to walk 10 meters (in seconds), both in ON-medication. A longer duration to perform the task represents a more impaired mobility. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Changes in Timed Up and Go (TUG) test Performance (sec) | Change in the duration to perform the Timed-Up and Go (TUG) test in seconds, with and without a cognitive dual task, in ON-medication. The Timed Up and Go performance is a measure of mobility, and a longer duration to perform the task represents a more impaired mobility. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Changes in 360° turning performance (sec) | Change in the duration to turn 360° in place in ON medication, with and without a cognitive dual task. A longer duration to perform the task represents a more impaired mobility. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Mean change in objective, unsupervised quantification of participant motor impairment, using motion sensors | Motor impairment will be determined based on recordings using five sensors (both arms and legs, and lower back) for the entire duration of the trial (PD Monitor, PD Neuroelectrics). Sensors will be placed before the SCS surgery and after each change in SCS parameter, up to the end of the open label phase (28 weeks). | Baseline, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Change in balance: objective measure of sway velocity on a force platform (metre/sec) | Sway will be measured on a force platform before and after each SCS parameter change, up to 28 weeks post-intervention. Sway metric (sway velocity) will be collected at each time point in five different conditions, namely while standing on an hard surface with eyes open (condition 1) and closed (condition 2), on a soft surface with eyes open (condition 3) and closed (condition 4), and while tandem standing with eyes open (condition 5). | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Changes in Non-motor Symptoms of PD | Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 
| Changes in Quality of Life Measured by a 39-item Parkinson's Disease Questionnaire (PDQ-39) | Parkinson's Disease Questionnaire - 39 (PDQ-39) is a self-administered questionnaire. It comprises of 39 questions, relating to eight key areas of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms in change from Baseline to end of Maintenance. | Baseline, day 1 post-surgery, week 6 post-surgery, week 12 post-surgery, week 18 post-surgery, week 28 post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Stimulation, Parkinson's, Gait Disorders