Clinical trial NCT05148468: 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
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson Disease
Gait Disorders, Neurologic
Keywords: gait
Parkinson´s disease
Spinal Cord stimulation
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2021-12-08
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double blinded randomized placebo controlled cross over study
Primary purpose: TREATMENT

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:

1. 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.
2. 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.
3. 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.

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)

Primary outcomes:
measure: Change on Timed Up and Go - Test 3 Meters (TUG-Test 3M)
timeFrame: 6 months
Secondary outcomes:
measure: Unified Parkinson's Disease Rating Scale (MDS-UPDRS) - Part III
timeFrame: 6 months
measure: Parkinson's Disease Questionnaire (PDQ39)
timeFrame: 6 months
measure: New Freezing of Gait Questionnaire (NFOG-Q)
timeFrame: 6 months
measure: 2 minute walk test
timeFrame: 6 months
measure: Mini Balance Evaluation Systems Test (Mini-BESTest)
timeFrame: 6 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da USP
state: SP
Study officials:
References:
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