Spinal Cord Stimulation for Freezing of Gait in Parkinson's Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age40-80
SponsorUniversitaire Ziekenhuizen KU Leuven
About this trial
Freezing of gait (FOG) is a severely disabling gait disorder in Parkinson's disease (PD). Its poor response to current therapies reflects the shortfall in current knowledge on its exact pathophysiology. Case series suggest a therapeutic promise of spinal cord stimulation (SCS) for FOG, but double-blind randomised controlled trials with reliable FOG assessments are lacking.
This randomised, double-blind, placebo-controlled cross-over trial aims to define the outcome, safety, optimal stimulation paradigm and underlying mechanism of SCS for FOG in PD, by exploring both clinical and neurophysiological parameters.
Twenty-nine PD patients with refractory FOG will receive an implanted SCS lead connected to an external trial stimulator. During a 3-week trial, 3 stimulation paradigms will be tested in random order, including one sham paradigm. SCS outcome on FOG will be evaluated through wearable accelerometers, self-reported questionnaires and a FOG-provoking protocol at home. Spinal electrophysiological recordings will compare neural properties between PD patients with and without FOG and evaluate intra-patient differences (e.g., on/off medication, DBS states). In patients with deep brain stimulation (DBS) including BrainSense technology, the effect of SCS on pathological beta oscillations in the STN will be explored. A subsequent long-term open-label phase will be conducted in those patients who desire a definitive implanted stimulator.
This project will provide new insights into the pathophysiology of FOG, pave the way for SCS implementation in clinical practice and enhance future patient selection.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of idiopathic PD in accordance with the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease
Optimal medical or DBS management for FOG, as evaluated by a movement disorder neurologist and programming expert. Stable PD medication and/or DBS settings for ≥ 1 month prior to baseline assessment and no changes are expected for the next 8 weeks
Self-reported FOG severity of ≥ 1 FOG episode per day, based on NFOG-Q items 1 and 2
Presence of FOG during in-hospital clinical assessment consisting of 3 FOG-provoking tasks, in the on-medication state
Disqualifiers
Presence of other severe neurological, psychiatric or other disorder that may impede assessment of outcomes
Contra-indications to SCS surgery (e.g. epidural fibrosis, inability to safely discontinue anticoagulant drugs, allergy to implants, medically inoperable)
Cognitive impairment (Montreal Cognitive Assessment (MOCA) <19/30)
Chronic (>6m) severe (numeric rating scale >5/10) back or leg pain, or FBSS, as the antalgic effect of SCS could cloud our interpretations for its effect on FOG
Trial design
Design model
Crossover
Treatments tested in this trial
Spinal Cord Stimulation
DeviceSCS is an established treatment for chronic neuropathic pain and the implantation procedure in this study follows the conventional clinical approach. Under local anaesthesia, a lead electrode is positioned in the spinal epidural space at the Th8-Th10 vertebral levels. The electrode is then connected to an external stimulator (implantable pulse generator, IPG), used for the 3-week external trial stimulation. Upon completion of the core trial, the electrode may either be removed or connected to an internal IPG, after extensive counselling and dependent on the FOG outcome and patient's preference. A subsequent long-term open label phase will evaluate the long-term efficacy and safety of SCS on FOG, with a follow-up period of six months. Electrophysiological recordings of the dorsal spinal cord will be conducted at the end of the external trial stimulation and at the 6-month follow-up.
Spinal electrophysiological recordings
Other interventionThe sole purpose of the control groups in this study, is to facilitate the interpretation of spinal cord electrophysiological characteristics in PD freezers by providing a comparison with individuals without the condition.
Treatment groups
29 Participants
are divided into 3 treatment groupsGroup A: PD patients with refractory FOGExperimental treatment 1 intervention
Group B: Control group 1: SCS patients without PDOther 1 intervention
Group C: Control group 2: SCS patients with PD, without FOGOther 1 intervention
Trial outcomes
Primary outcomes
1
FOG-provoking protocol
The total percentage time frozen (%TF) of all FOG manifestations across all gait tasks of the FOG-protocol performed in the off medication state, compared between the different SCS paradigms.
Time frame
Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.Secondary outcomes
1
Safety
Adverse event (AE) frequency, severity and causality
Time frame
6 months2
FOG-provoking protocol
The total %TF of all FOG manifestations across all gait tasks of the FOG-protocol performed in the on medication state, compared between the different SCS paradigms.
Time frame
Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.3
FOG-provoking protocol
The %TF in both off- and on medication states for the different FOG manifestations, and for each of the different gait tasks of the FOG-protocol, compared between the different SCS paradigms.
Time frame
Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.4
Changes in home-based gait function
Objective assessment of changes in gait quantity and quality during daily life at home, using biometric data collected by a wearable accelerometer throughout the core trial. Data will be compared across the different SCS paradigms to evaluate their impact on everyday gait performance.
Time frame
Core-trial: 3 weeksOther outcomes
1
STN-LFP recordings
(1) Changes in LFP spectrum (e.g. β activity) and (2) possible correlations with FOG alleviation, measured in patients with STN-DBS (Medtronic Percept PC) during the FOG-provoking protocol.
Time frame
Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.2
Spinal electrophysiological recordings
Changes in spinal cord electrophysiological characteristics, * (1) compared between PD freezers whose FOG responds to SCS and those whose FOG does not respond to SCS (in all 29 patients of the intervention group, at the end of the trial stimulation). * (2) Compared between on- and off medication state, and between DBS-on and DBS-off state (in PD freezers from the intervention group who received a permanent SCS implant, at 6 month follow-up; and in control group 2). * (3) compared between PD freezers (from the intervention group who received a permanent SCS implant, at 6 month follow-up), SCS patients without PD (control group 1) and SCS patients with PD but without FOG (control group 2).
Time frame
at 3 weeks and at 6 monthsSponsors and contacts
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Source ClinicalTrials.gov