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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease; a Randomized, Crossover, Double Blinded, Placebo-Controlled Study

Conditions
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Parkinson Disease, Gait Disorders, Neurologic

Intervention / Treatment
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* Device: Active spinal cord stimulation
* Device: Sham spinal cord stimulation


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double blinded randomized placebo controlled cross over study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br>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. | Device: Active spinal cord stimulation<br>* 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.<br>|
| Sham Comparator: Sham stimulation<br>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. | Device: Sham spinal cord stimulation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 
| 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. | 6 months | 
| 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. | 6 months | 
| 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. | 6 months | 
| 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. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gait, Parkinson´s disease, Spinal Cord stimulation