Spinal Cord Stimulation for Gait Dysfunction in Parkinson's Disease (SCORE-PD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Freezing of Gait
• Intervention / Treatment: Device: Spinal Cord Stimulation - High Frequency SCS; Device: Spinal Cord Stimulation - Burst SCS; Device: Spinal Cord Stimulation - Sham SCS

Detailed Description

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:

1. Burst stimulation
2. High frequency stimulation
3. 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.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yen Tai; Phone Number: +442033111182; Email: yen.tai@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Imperial College London
    • Contact: Matteo Ciocca; Email: m.ciocca20@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Yen Tai, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Spinal Cord Stimulation; Gait Disorders; Parkinson's
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 22CX7894

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Group data can be made available upon request, following completion and publication of results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes