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Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease

Primary Purpose

Parkinson Disease, Gait Disorders, Neurologic

Status
Active
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Active spinal cord stimulation
Sham spinal cord stimulation
Sponsored by
University of Sao Paulo General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring gait, Parkinson´s disease, Spinal Cord stimulation

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosed Parkinson´s Disease with Hoehn Yahr scale between 2,5 and 4,0
  • Main complaint of balance or freezing of gait
  • Score of 2 or more on subitem 3.11 of the MDS UPDRS scale concerning Freezing of Gait severity.
  • Capable of informed consent

Exclusion Criteria:

  • Frequent lower limb, lower back or hip pain scoring 3 or more on visual analog scale
  • Uncontrolled or serious comorbidities such as uncontrolled diabetes mellitus, renal disease, anticoagulation, immunosuppression or other medical conditions that present a contraindication for SCS surgery
  • Psychosis, uncontrolled depression (BDI >14) or anxiety disorder (BAI >14)

Sites / Locations

  • Hospital das Clínicas da Faculdade de Medicina da USP

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active stimulation

Sham stimulation

Arm Description

During active stimulation phase, patients will receive through the spinal cord stimulator active tonic stimulation with amplitude set to 90% of paresthesia inducing threshold, therefore allowing blinding. Patients will be evaluated after a two week wash out period with no stimulation and after two weeks of continuous active stimulation.

During sham stimulation phase, patients will receive through the spinal cord stimulator a zero amplitude stimulation, therefore having no electrical current passing through epidural leads but with the program status still displayed as "on" if checked with patient's personal controller. Patients will be evaluated after a two week wash out period with no stimulation and after two weeks of continuous sham stimulation.

Outcomes

Primary Outcome Measures

Change on Timed Up and Go - Test 3 Meters (TUG-Test 3M)
Comparison of the change in Timed Up and Go test times between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting.

Secondary Outcome Measures

Unified Parkinson's Disease Rating Scale (MDS-UPDRS) - Part II and III
Comparison of change in Unified Parkinson's Disease Rating Scale score part II and III between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. MDS-PDRS part II is scored from 0 to 52 with higher scores associated with worse motor related daily activities performance. MDS-UPDRS part III is scored from 0 to 132 with higher scores associated with worse motor performance in parkinson related tests.
Parkinson's Disease Questionnaire (PDQ39)
Comparison of change in Parkinson's Disease Questionnaire 39 (PDQ-39) between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. PDQ39 is score from 0 to 100%, higher values are associated with worse quality of life.
New Freezing of Gait Questionnaire (NFOG-Q)
Comparison of change in New Freezing of Gait Questionnaire (NFOG-Q) score between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. NFOG-Q is scored from 0 to 28, higher values are associated with more freezing of gait.
2 minute walk test
Comparison of change in gait speed change in 2 minute walk test between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. Lower values correlate with better gait speed and mobility.
Mini Balance Evaluation Systems Test (Mini-BESTest)
Comparison of change in Mini Balance Evaluation Systems Test (Mini-BESTest) test scores between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. Minimum value 0 and maximum value 108. Higher value is associated with better balance.

Full Information

First Posted
November 4, 2021
Last Updated
May 8, 2023
Sponsor
University of Sao Paulo General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05148468
Brief Title
Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease
Official Title
Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease; a Randomized, Crossover, Double Blinded, Placebo-Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
November 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sao Paulo General Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Spinal cord stimulation (SCS) for Parkinson´s disease (PD) has been studied for a decade but consensus on efficacy is still lacking, with the previous stimulation standard paresthesia inducing threshold hampering adequate subject blinding. Considering that tonic stimulation for pain has been shown to be efficacious for most patients on subthreshold stimulation parameters we hypothesize a similar result with it´s use on PD. The investigators aim to: Produce stronger evidence on SCS efficacy for PD in regards to gait, motor scores and quality of life measures by incorporating subthreshold in a randomized cross over placebo-controlled study with a large sample. Identify predictors of good response to SCS therapy by performing trans spinal magnetic stimulation (TSMS) before SCS implant and correlating the response to SCS to that of the noninvasive TSMS. Better provide biomarkers of SCS therapy through functional magnetic resonance imaging and electroencephalographic mapping.
Detailed Description
Gait impairment in Parkinson´s Disease (PD) is often refractory to standard medication therapy and functional surgery options currently explored resulting in grave loss of independence and quality of life. Spinal cord stimulation (SCS) has been explored for its role in PD after enthusiastic animal studies and despite mixed initial results is currently a very promising candidate for ameliorating hard to treat gait and balance disorders. Consensus on tonic SCS efficacy is hampered mostly due to small samples and lack of randomized controlled trials so far, and the impossibility of subject blinding due to standard stimulation settings using currents over the paresthesia inducing threshold. Some small studies already attempted subthreshold blinding and all resulted in non significant results, however with no important difference when switching to suprathreshold settings, thus raising the possibility of non responder subjects or inefficient therapy and calling for additional exploration. The investigators aim to explore the feasibility of a placebo controlled trial using subthreshold stimulation with a larger sample and produce stronger evidence on SCS efficacy for PD. Additionally, the possibility of non responder subjects will be explored by correlating the degree of response to SCS to patient demographic characteristics including age, PD severity and cognition, gait characteristics and the degree of response to trans spinal magnetic stimulation (TSMS), a non invasive magnetic stimulation of upper thoracic spinal region, aiming to identify prognostic factors for the therapy. Finally, functional magnetic resonance imaging and electroencephalographic mapping will be performed in order to identify biomarkers of SCS therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Gait Disorders, Neurologic
Keywords
gait, Parkinson´s disease, Spinal Cord stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Double blinded randomized placebo controlled cross over study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Patients and examiners will be blinded to stimulation status
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active stimulation
Arm Type
Experimental
Arm Description
During active stimulation phase, patients will receive through the spinal cord stimulator active tonic stimulation with amplitude set to 90% of paresthesia inducing threshold, therefore allowing blinding. Patients will be evaluated after a two week wash out period with no stimulation and after two weeks of continuous active stimulation.
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
During sham stimulation phase, patients will receive through the spinal cord stimulator a zero amplitude stimulation, therefore having no electrical current passing through epidural leads but with the program status still displayed as "on" if checked with patient's personal controller. Patients will be evaluated after a two week wash out period with no stimulation and after two weeks of continuous sham stimulation.
Intervention Type
Device
Intervention Name(s)
Active spinal cord stimulation
Intervention Description
Spinal cord stimulation is acomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During active stimulation amplitude will be set to 90% paresthesia inducing threshold.
Intervention Type
Device
Intervention Name(s)
Sham spinal cord stimulation
Intervention Description
Spinal cord stimulation is acomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During sham stimulation amplitude will be set to zero.
Primary Outcome Measure Information:
Title
Change on Timed Up and Go - Test 3 Meters (TUG-Test 3M)
Description
Comparison of the change in Timed Up and Go test times between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Unified Parkinson's Disease Rating Scale (MDS-UPDRS) - Part II and III
Description
Comparison of change in Unified Parkinson's Disease Rating Scale score part II and III between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. MDS-PDRS part II is scored from 0 to 52 with higher scores associated with worse motor related daily activities performance. MDS-UPDRS part III is scored from 0 to 132 with higher scores associated with worse motor performance in parkinson related tests.
Time Frame
6 months
Title
Parkinson's Disease Questionnaire (PDQ39)
Description
Comparison of change in Parkinson's Disease Questionnaire 39 (PDQ-39) between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. PDQ39 is score from 0 to 100%, higher values are associated with worse quality of life.
Time Frame
6 months
Title
New Freezing of Gait Questionnaire (NFOG-Q)
Description
Comparison of change in New Freezing of Gait Questionnaire (NFOG-Q) score between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. NFOG-Q is scored from 0 to 28, higher values are associated with more freezing of gait.
Time Frame
6 months
Title
2 minute walk test
Description
Comparison of change in gait speed change in 2 minute walk test between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. Lower values correlate with better gait speed and mobility.
Time Frame
6 months
Title
Mini Balance Evaluation Systems Test (Mini-BESTest)
Description
Comparison of change in Mini Balance Evaluation Systems Test (Mini-BESTest) test scores between ON-stimulation and baseline and sham-stimulation and baseline in double blinded setting. Minimum value 0 and maximum value 108. Higher value is associated with better balance.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed Parkinson´s Disease with Hoehn Yahr scale between 2,5 and 4,0 Main complaint of balance or freezing of gait Score of 2 or more on subitem 3.11 of the MDS UPDRS scale concerning Freezing of Gait severity. Capable of informed consent Exclusion Criteria: Frequent lower limb, lower back or hip pain scoring 3 or more on visual analog scale Uncontrolled or serious comorbidities such as uncontrolled diabetes mellitus, renal disease, anticoagulation, immunosuppression or other medical conditions that present a contraindication for SCS surgery Psychosis, uncontrolled depression (BDI >14) or anxiety disorder (BAI >14)
Facility Information:
Facility Name
Hospital das Clínicas da Faculdade de Medicina da USP
City
São Paulo
State/Province
SP
ZIP/Postal Code
05403000
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease

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