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

NCT06798844 | Recruiting Phase 2 DMC FDA Device

• 3 other identifiers: S69667CIV-24-10-049614402173
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Freezing of Gait; Parkinson Disease

Keywords

Spinal Cord Stimulation; Freezing of Gait; Parkinson disease

Outcome Measures

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.

  Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.

Secondary Outcomes (19)

• Safety

  6 months

• FOG-provoking protocol

  Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.

• FOG-provoking protocol

  Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.

• Changes in home-based gait function

  Core-trial: 3 weeks

• Patient Global Impression of Improvement (PGI-I)

  Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.

Other Outcomes (2)

• STN-LFP recordings

  Core trial: day 7, 14 and 21 post-surgery. Long-term: at 6 months follow-up.

• Spinal electrophysiological recordings

  at 3 weeks and at 6 months

Study Arms (3)

PD patients with refractory FOG

EXPERIMENTAL

29 PD patients with refractory FOG will receive a 3-week SCS trial with an implanted lead connected to an external stimulator, during which two SCS paradigms (one with and one without paraesthesia) and a sham paradigm will be compared. If a clinically relevant improvement in FOG or gait is perceived during the external trial stimulation, the participant will receive a permanent implanted neurostimulator.

Device: Spinal Cord Stimulation

Control group 1: SCS patients without PD

OTHER

± 15 patients without PD who received SCS for FBSS outside research settings. To evaluate the secondary exploratory outcome on spinal cord electrophysiology in PD freezers, two control groups of SCS patients treated for approved indications outside research settings will be included. This allows for an exploratory, non-blinded, and non-randomized comparison of spinal cord electrophysiological characteristics between patients with PD and FOG (intervention group), without PD (control group 1) and with PD without FOG (control group 2).

Other: Spinal electrophysiological recordings

Control group 2: SCS patients with PD, without FOG

OTHER

Max. 5 patients with PD without FOG who received SCS for FBSS outside research settings. To evaluate the secondary exploratory outcome on spinal cord electrophysiology in PD freezers, two control groups of SCS patients treated for approved indications outside research settings will be included. This allows for an exploratory, non-blinded, and non-randomized comparison of spinal cord electrophysiological characteristics between patients with PD and FOG (intervention group), without PD (control group 1) and with PD without FOG (control group 2).

Other: Spinal electrophysiological recordings

Interventions

Spinal Cord Stimulation DEVICE

SCS 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.

Also known as: Medtronic Inceptiv neurostimulator

PD patients with refractory FOG

Spinal electrophysiological recordings OTHER

The 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.

Control group 1: SCS patients without PD; Control group 2: SCS patients with PD, without FOG

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Able to walk 10 meters unassisted without a walking aid (use of a cane is allowed)
• Able to understand study requirements and provide consent
• Age 40-79 years inclusive

You may not qualify if:

• 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
• Duodopa pump or apomorphine injections
• Fall frequency \>1x/day (this criterion comprises only 'actual falls', no 'near falls')
• Absence of FOG during preoperative at-home FOG-protocol, in on- or off-medication assessment
• Pregnancy, lactating or active pregnancy plans

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Spinal Cord Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation

Study Officials

• Philippe De Vloo, MD, PhD, Prof.

  Department of Neurosurgery, University Hospitals Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Smeets, MD

CONTACT

+32 16 344290; sara.smeets@uzleuven.be

Amal El Kaddouri

CONTACT

+32 16 344801; amal.elkaddouri@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both the patient and assessors will be blinded to the SCS paradigm during the core trial. Upon the patient's completion of the core trial (the 3-week trial stimulation period) and after blinded assessment of all videos, the investigator will be unblinded to the patient's treatment response to evaluate the effect of SCS on FOG. This information is critical for determining, in consultation with the patient, whether to proceed with the implantation of a definitive internal neurostimulator or to remove the trial electrode. It is important to note that, as previously stated, the investigator and assessors remain blinded to the patient's assigned SCS paradigm throughout the whole core trial.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sham-controlled randomized double-blinded cross-over study

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: January 29, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 13, 2025

Record last verified: 2025-01

Locations

BE (1)