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

Victor S Hvingelby; Miriam Højholt Terkelsen; Erik L Johnsen; Mette Møller; Erik Hvid Danielsen; Tove Henriksen; Andreas Nørgaard Glud; Yen Tai; Anne Sofie Møller Andersen; Kaare Meier; Per Borghammer; Elena Moro; Jens Christian Hedemann Sørensen; Nicola Pavese

doi:10.1136/bmjno-2022-000333

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

Victor S Hvingelby, Miriam Højholt Terkelsen, Erik L Johnsen, Mette Møller, Erik Hvid Danielsen, Tove Henriksen, Andreas Nørgaard Glud, Yen Tai, Anne Sofie Møller Andersen, Kaare Meier, Per Borghammer, Elena Moro, Jens Christian Hedemann Sørensen, Nicola Pavese^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

4 Citations (Scopus)

Abstract

Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and 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 aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.

Methods and analysis: A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months.

Ethics and dissemination: This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.

Trial registration number: NCT05110053; ClinicalTrials.gov Identifier.

Original language	English
Article number	e000333
Journal	BMJ Neurology Open
Volume	4
Issue	2
ISSN	2632-6140
DOIs	https://doi.org/10.1136/bmjno-2022-000333
Publication status	Published - Aug 2022

Keywords

ELECTRICAL STIMULATION
GAIT
PARKINSON'S DISEASE
RANDOMISED TRIALS

Access to Document

10.1136/bmjno-2022-000333Licence: CC BY-NC

Cite this

Hvingelby, V. S., Højholt Terkelsen, M., Johnsen, E. L., Møller, M., Danielsen, E. H., Henriksen, T., Glud, A. N., Tai, Y., Møller Andersen, A. S., Meier, K., Borghammer, P., Moro, E., Sørensen, J. C. H., & Pavese, N. (2022). 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 Neurology Open, 4(2), Article e000333. https://doi.org/10.1136/bmjno-2022-000333

@article{d857db37e3864fcbb7d87d1a2c9f914e,

title = "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",

abstract = "Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and 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 aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysis: A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months. Ethics and dissemination: This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number: NCT05110053; ClinicalTrials.gov Identifier.",

keywords = "ELECTRICAL STIMULATION, GAIT, PARKINSON'S DISEASE, RANDOMISED TRIALS",

author = "Hvingelby, {Victor S} and {H{\o}jholt Terkelsen}, Miriam and Johnsen, {Erik L} and Mette M{\o}ller and Danielsen, {Erik Hvid} and Tove Henriksen and Glud, {Andreas N{\o}rgaard} and Yen Tai and {M{\o}ller Andersen}, {Anne Sofie} and Kaare Meier and Per Borghammer and Elena Moro and S{\o}rensen, {Jens Christian Hedemann} and Nicola Pavese",

note = "{\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = aug,

doi = "10.1136/bmjno-2022-000333",

language = "English",

volume = "4",

journal = "BMJ Neurology Open",

issn = "2632-6140",

publisher = "BMJ Publishing Group",

number = "2",

}

Hvingelby, VS , Højholt Terkelsen, M , Johnsen, EL, Møller, M, Danielsen, EH, Henriksen, T, Glud, AN, Tai, Y, Møller Andersen, AS , Meier, K , Borghammer, P, Moro, E, Sørensen, JCH & Pavese, N 2022, '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 Neurology Open, vol. 4, no. 2, e000333. https://doi.org/10.1136/bmjno-2022-000333

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. / Hvingelby, Victor S ; Højholt Terkelsen, Miriam ; Johnsen, Erik L et al.
In: BMJ Neurology Open, Vol. 4, No. 2, e000333, 08.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Spinal cord stimulation therapy for patients with Parkinson's disease and gait problems (STEP-PD)

T2 - study protocol for an exploratory, double-blind, randomised, placebo-controlled feasibility trial

AU - Hvingelby, Victor S

AU - Højholt Terkelsen, Miriam

AU - Johnsen, Erik L

AU - Møller, Mette

AU - Danielsen, Erik Hvid

AU - Henriksen, Tove

AU - Glud, Andreas Nørgaard

AU - Tai, Yen

AU - Møller Andersen, Anne Sofie

AU - Meier, Kaare

AU - Borghammer, Per

AU - Moro, Elena

AU - Sørensen, Jens Christian Hedemann

AU - Pavese, Nicola

PY - 2022/8

Y1 - 2022/8

N2 - Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and 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 aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysis: A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months. Ethics and dissemination: This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number: NCT05110053; ClinicalTrials.gov Identifier.

AB - Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and 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 aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysis: A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months. Ethics and dissemination: This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number: NCT05110053; ClinicalTrials.gov Identifier.

KW - ELECTRICAL STIMULATION

KW - GAIT

KW - PARKINSON'S DISEASE

KW - RANDOMISED TRIALS

U2 - 10.1136/bmjno-2022-000333

DO - 10.1136/bmjno-2022-000333

M3 - Journal article

C2 - 36101543

SN - 2632-6140

VL - 4

JO - BMJ Neurology Open

JF - BMJ Neurology Open

IS - 2

M1 - e000333

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this