Spinal Cord sTimulation thEraPy for Parkinson's Disease Patients With Gait Problems

NCT05110053 | Completed DMC FDA Device

• 1 other identifier: STEP-PD-449
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. No treatment is available for these symptoms. Spinal Cord Stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of PD patients. The mechanism of action is unclear and some patients are nonresponders. With this double-blind placebo-controlled proof of concept and feasibility imaging study, we aim to shed light on the mechanism of action of SCS and collect data to inform development of a scientifically sound clinical trial protocol. We also hope to identify imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection. Patients will be assessed with clinical rating scales and gait evaluations at baseline and 6 and 12 months after SCS. They will also receive serial 18F-FDG and (\[18F\]FEOBV) PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function

Conditions

Parkinson Disease; Gait Disorders, Neurologic; Fall Injury

Outcome Measures

Primary Outcomes (4)

• Clinical improvement of gait

  To establish proof of concept by changes in Postural Instability and Gait Difficulty (PIGD) subscore of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS). This subscore is the sum of 2.12 (Walking and balance), 2.13 (Freezing), 3.10 (Gait), 3.11 (Freezing of gait) and 3.12 (Postural stability)

  Follow-up at 6 and 12 months

• Changes in resting metabolic networks assessed with 18-FDG PET/CT

  18-FDG is a tracer characterizing glucose metabolism. Quantification of 18F-FDG PET scans will be performed. Analysis of PET scans will be performed using both a region of interest (ROI) approach sampling hypothesized areas and exploratory Statistical Parametric Mapping (SPM). For each subject, ROIs will be defined on the individual CT and copied onto co-registered PET images. ROIs will include putamen, caudate nuclei, ventral striatum, thalamus, red nucleus, amygdala, hypothalamus, locus coeruleus, median raphe and the ventral tegmental area. SPM will allow automated interrogation of parametric images across the whole brain volume at a voxel level to localize significant differences in tracer uptake without a priori selection of target regions. The primary end points are the between-group differences in striatal and extrastriatal tracer uptake/binding.

  Follow-up at 6 and 12 months

• Changes in brain cholinergic function

  (\[18F\]FEOBV) PET is an in vivo marker of the brain vesicular acetylcholine transporter (VAChT) and provides information of the integrity of the brain cholinergic neurotransmitter system. Quantification of 18FEOBV scans will be performed. Analysis of PET scans will be performed using both a region of interest (ROI) approach sampling hypothesized areas and exploratory Statistical Parametric Mapping (SPM). For each subject, ROIs will be defined on the individual CT and copied onto co-registered PET images. ROIs will include putamen, caudate nuclei, ventral striatum, thalamus, red nucleus, amygdala, hypothalamus, locus coeruleus, median raphe and the ventral tegmental area. SPM will allow automated interrogation of parametric images across the whole brain volume at a voxel level to localize significant differences in tracer uptake without a priori selection of target regions. The primary end points are the between-group differences in striatal and extrastriatal tracer uptake/binding.

  Follow-up at 6 and 12 months

• Adverse events

  Evaluation of the safety and tolerability of SCS treatment in patients with PD. Measured as type, frequency and severity of adverse events.

  6 and 12 months

Secondary Outcomes (9)

• subjective changes in quality of life per SF-36

  Follow-up at 6 and 12 months

• subjective changes in parkinsons specific quality of life

  Follow-up at 6 and 12 months

• Clinical improvement of gait as measured by TUG in s

  Follow-up at 6 and 12 months

• subjective changes in gait function

  Follow-up at 6 and 12 months

• subjective changes in occurence of freezing

  Follow-up at 6 and 12 months

Study Arms (2)

Active

ACTIVE COMPARATOR

All patients will receive surgery with implantation of a SCS device. Patients randomized to the active arm, will receive active stimulation. Blinding will continue for 6 months, followed by a 6 month voluntary open-phase, active extension.

Device: Spinal Cord Stimulation

Placebo

PLACEBO COMPARATOR

All patients will receive surgery with implantation of a SCS device. Patients randomized to the placebo-arm of the trial will have the device switched off. Blinding will continue for 6 months, followed by a 6 month voluntary open-phase, active extension.

Device: Spinal Cord Stimulation

Interventions

Spinal Cord Stimulation DEVICE

Spinal Cord stimulation. Surgery is done in local anaesthesia. A small electrode is placed in the epidural space corresponding approximately at the Th8-Th10 level. An impulsegenerator, connected to the electrode, is placed in the subcutaneus fat in the gluteal region.

Active; Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Idiopathic PD diagnosed by a movement disorders neurologist
• Presence of gait functional impairment despite optimal medical management
• Able to walk independently without an aid for a minimum of two minutes without rest
• Absence of secondary causes of gait problems
• Able to understand study requirements - able to provide consent
• Above 50 years of age

You may not qualify if:

• The presence of another significant neurological/psychiatric disorder or significant disease
• Spinal anatomical abnormalities precluding SCS surgery
• History of stroke or structural lesions on CT that could interfere with image analysis.
• History of chronic pain and severe degenerative spine disease with or without chronic pain
• History of drug addiction or dependency
• Previous DBS surgery for PD
• Pregnancy or breast-feeding.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University

Aarhus, 8200, Denmark

Location

Related Publications (2)

• Terkelsen MH, Hvingelby VS, Johnsen EL, Moller M, Danielsen EH, Henriksen T, Glud AN, Tai Y, Baun AM, Knudsen AL, Valdemarsen RN, Horsager J, Okkels N, Andersen ASM, Meier K, Borghammer P, Molloy S, Nandi D, Moro E, Sorensen JCH, Pavese N. Spinal cord stimulation therapy for gait impairment in Parkinson's disease: a double-blinded, randomised feasibility trial with an open extension. Nat Commun. 2026 Jan 29. doi: 10.1038/s41467-026-68782-w. Online ahead of print.

  PMID: 41611672 DERIVED

• Hvingelby VS, Hojholt Terkelsen M, Johnsen EL, Moller M, Danielsen EH, Henriksen T, Glud AN, Tai Y, Moller Andersen AS, Meier K, Borghammer P, Moro E, Sorensen JCH, Pavese N. Spinal cord stimulation therapy for patients with Parkinson's disease and gait problems (STEP-PD): study protocol for an exploratory, double-blind, randomised, placebo-controlled feasibility trial. BMJ Neurol Open. 2022 Aug 24;4(2):e000333. doi: 10.1136/bmjno-2022-000333. eCollection 2022.

  PMID: 36101543 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic

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; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation

Study Officials

• Nicola Pavese, MD, PhD, FRCP, FEAN

  University of Aarhus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Following surgery with implantation of Spinal cord stimulator (SCS), participants will be randomized to either active or placebo stimulation. The patient will have no knowledge of group, as the stimulation protocol is designed to be subperceptional. Further, the primary investigators and outcome assessors will be blinded to group assignment. Imaging analysis will likewise be blinded to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded, placebo-controlled intervention study with six month voluntary, active extension.

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: November 5, 2021
• Study Start: September 1, 2021
• Primary Completion: October 1, 2023
• Study Completion: June 1, 2024
• Last Updated: May 23, 2025

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Upon request
• Access Criteria: Based on relevant request to a principal investigator

Locations

DK (1)