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

NCT05148468 | Terminated DMC FDA Device

• 1 other identifier: SCSPDgait
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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. 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. 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. 3.Better provide biomarkers of SCS therapy through functional magnetic resonance imaging and electroencephalographic mapping.

Conditions

Parkinson Disease; Gait Disorders, Neurologic

Keywords

gait; Parkinson´s disease; Spinal Cord stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Unified Parkinson's Disease Rating Scale (MDS-UPDRS) - Part III

  6 months

• Parkinson's Disease Questionnaire (PDQ39)

  6 months

• New Freezing of Gait Questionnaire (NFOG-Q)

  6 months

• 2 minute walk test

  6 months

• Mini Balance Evaluation Systems Test (Mini-BESTest)

  6 months

Study Arms (2)

Active stimulation

EXPERIMENTAL

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 three week wash out period with no stimulation and after three weeks of continuous active stimulation.

Device: Active spinal cord stimulation

Sham stimulation

SHAM COMPARATOR

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 three week wash out period with no stimulation and after three weeks of continuous sham stimulation.

Device: Sham spinal cord stimulation

Interventions

Active spinal cord stimulation DEVICE

Spinal cord stimulation is accomplished 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.

Active stimulation

Sham spinal cord stimulation DEVICE

Spinal cord stimulation is accomplished 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.

Sham stimulation

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

Hospital das Clínicas da Faculdade de Medicina da USP

São Paulo, São Paulo, 05403000, Brazil

Location

Related Publications (20)

• Agari T, Date I. Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson's disease. Neurol Med Chir (Tokyo). 2012;52(7):470-4. doi: 10.2176/nmc.52.470.

  PMID: 22850494 BACKGROUND

• Fuentes R, Petersson P, Nicolelis MA. Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach. Eur J Neurosci. 2010 Oct;32(7):1100-8. doi: 10.1111/j.1460-9568.2010.07417.x.

  PMID: 21039949 BACKGROUND

• de Andrade EM, Ghilardi MG, Cury RG, Barbosa ER, Fuentes R, Teixeira MJ, Fonoff ET. Spinal cord stimulation for Parkinson's disease: a systematic review. Neurosurg Rev. 2016 Jan;39(1):27-35; discussion 35. doi: 10.1007/s10143-015-0651-1. Epub 2015 Jul 30.

  PMID: 26219854 BACKGROUND

• Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson's disease. Science. 2009 Mar 20;323(5921):1578-82. doi: 10.1126/science.1164901.

  PMID: 19299613 BACKGROUND

• Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, Brown P. Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology. 2010 Apr 20;74(16):1325-7. doi: 10.1212/WNL.0b013e3181d9ed58. No abstract available.

  PMID: 20404313 BACKGROUND

• Fenelon G, Goujon C, Gurruchaga JM, Cesaro P, Jarraya B, Palfi S, Lefaucheur JP. Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease. Parkinsonism Relat Disord. 2012 Feb;18(2):213-4. doi: 10.1016/j.parkreldis.2011.07.015. Epub 2011 Aug 23. No abstract available.

  PMID: 21865071 BACKGROUND

• Santana MB, Halje P, Simplicio H, Richter U, Freire MAM, Petersson P, Fuentes R, Nicolelis MAL. Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease. Neuron. 2014 Nov 19;84(4):716-722. doi: 10.1016/j.neuron.2014.08.061. Epub 2014 Oct 30.

  PMID: 25447740 BACKGROUND

• Pinto de Souza C, Hamani C, Oliveira Souza C, Lopez Contreras WO, Dos Santos Ghilardi MG, Cury RG, Reis Barbosa E, Jacobsen Teixeira M, Talamoni Fonoff E. Spinal cord stimulation improves gait in patients with Parkinson's disease previously treated with deep brain stimulation. Mov Disord. 2017 Feb;32(2):278-282. doi: 10.1002/mds.26850. Epub 2016 Nov 10.

  PMID: 27862267 BACKGROUND

• Akiyama H, Nukui S, Akamatu M, Hasegawa Y, Nishikido O, Inoue S. Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson's disease: a case report. BMC Neurol. 2017 Aug 3;17(1):148. doi: 10.1186/s12883-017-0926-y.

  PMID: 28774283 BACKGROUND

• Samotus O, Parrent A, Jog M. Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients. Mov Disord. 2018 May;33(5):783-792. doi: 10.1002/mds.27299. Epub 2018 Feb 14.

  PMID: 29442369 BACKGROUND

• de Lima-Pardini AC, Coelho DB, Souza CP, Souza CO, Ghilardi MGDS, Garcia T, Voos M, Milosevic M, Hamani C, Teixeira LA, Fonoff ET. Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait. Elife. 2018 Aug 2;7:e37727. doi: 10.7554/eLife.37727.

  PMID: 30070204 BACKGROUND

• Kobayashi R, Kenji S, Taketomi A, Murakami H, Ono K, Otake H. New mode of burst spinal cord stimulation improved mental status as well as motor function in a patient with Parkinson's disease. Parkinsonism Relat Disord. 2018 Dec;57:82-83. doi: 10.1016/j.parkreldis.2018.07.002. Epub 2018 Jul 6.

  PMID: 30017249 BACKGROUND

• Mazzone P, Viselli F, Ferraina S, Giamundo M, Marano M, Paoloni M, Masedu F, Capozzo A, Scarnati E. High Cervical Spinal Cord Stimulation: A One Year Follow-Up Study on Motor and Non-Motor Functions in Parkinson's Disease. Brain Sci. 2019 Apr 3;9(4):78. doi: 10.3390/brainsci9040078.

  PMID: 30987170 BACKGROUND

• Hubsch C, D'Hardemare V, Ben Maacha M, Ziegler M, Patte-Karsenti N, Thiebaut JB, Gout O, Brandel JP. Tonic spinal cord stimulation as therapeutic option in Parkinson disease with axial symptoms: Effects on walking and quality of life. Parkinsonism Relat Disord. 2019 Jun;63:235-237. doi: 10.1016/j.parkreldis.2019.02.044. Epub 2019 Mar 2.

  PMID: 30852148 BACKGROUND

• Chakravarthy KV, Chaturvedi R, Agari T, Iwamuro H, Reddy R, Matsui A. Single arm prospective multicenter case series on the use of burst stimulation to improve pain and motor symptoms in Parkinson's disease. Bioelectron Med. 2020 Sep 28;6:18. doi: 10.1186/s42234-020-00055-3. eCollection 2020.

  PMID: 33005705 BACKGROUND

• Lai Y, Pan Y, Wang L, Zhang C, Sun B, Li D. Spinal Cord Stimulation with Surgical Lead Improves Pain and Gait in Parkinson's Disease after a Dislocation of Percutaneous Lead: A Case Report. Stereotact Funct Neurosurg. 2020;98(2):104-109. doi: 10.1159/000505707. Epub 2020 Feb 25.

  PMID: 32097953 BACKGROUND

• Prasad S, Aguirre-Padilla DH, Poon YY, Kalsi-Ryan S, Lozano AM, Fasano A. Spinal Cord Stimulation for Very Advanced Parkinson's Disease: A 1-Year Prospective Trial. Mov Disord. 2020 Jun;35(6):1082-1083. doi: 10.1002/mds.28065. Epub 2020 Apr 20. No abstract available.

  PMID: 32311155 BACKGROUND

• Cury RG, Carra RB, Capato TTC, Teixeira MJ, Barbosa ER. Spinal Cord Stimulation for Parkinson's Disease: Dynamic Habituation as a Mechanism of Failure? Mov Disord. 2020 Oct;35(10):1882-1883. doi: 10.1002/mds.28271. No abstract available.

  PMID: 33068473 BACKGROUND

• Samotus O, Parrent A, Jog M. Long-term update of the effect of spinal cord stimulation in advanced Parkinson's disease patients. Brain Stimul. 2020 Sep-Oct;13(5):1196-1197. doi: 10.1016/j.brs.2020.06.004. Epub 2020 Jun 3. No abstract available.

  PMID: 32504828 BACKGROUND

• Reis Menezes J, Bernhart Carra R, Aline Nunes G, da Silva Simoes J, Jacobsen Teixeira M, Paiva Duarte K, Ciampi de Andrade D, Barbosa ER, Antonio Marcolin M, Cury RG. Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease. J Clin Neurosci. 2020 Nov;81:306-309. doi: 10.1016/j.jocn.2020.10.001. Epub 2020 Oct 20.

  PMID: 33222935 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients and examiners will be blinded to stimulation status
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded randomized placebo controlled cross over study

Study Record Dates

• First Submitted: November 4, 2021
• First Posted: December 8, 2021
• Study Start: November 30, 2021
• Primary Completion: January 10, 2024
• Study Completion: March 1, 2024
• Last Updated: May 13, 2024

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)