Spinal Cord Stimulation for Gait in Parkinson Disease

Parkinson Disease Clinical Trial

Official title:

Thoracic Dorsal Spinal Cord Stimulation for the Treatment of Gait and Balance Impairments in Parkinson Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03079310
• Other study ID #: 107451
• Status: Recruiting
• Phase: N/A
• Start date: February 2016
• Est. completion date: April 2022

Study information

• Verified date: June 2020
• Source: Western University, Canada
• Contact: Mandar Jog, MD
• Phone: 519-685-8500
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Balance and gait impairment increases the risk of falls and contributes to a reduced quality of life and shorter survival in Parkinson disease (PD) and atypical Parkinsonism patients. In preliminary case studies, electrical epidural spinal cord stimulation (SCS) has been shown to significantly improve gait, postural instability, rigidity, and tremor. Controlled studies for optimizing which stimulation settings produce the best clinical response for mobility and gait, and achieving these results chronically are all significant unmet needs. Using quantitative laboratory and mobile technologies to test a range of stimulation settings, this research study aims to determine which SCS parameters or combination of parameters is best suited to effectively alleviate disabling symptoms experienced by each patient.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: April 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Consenting male and female participants, aged 18 years to 80 years

• Idiopathic PD with II-IV Hoehn-Yahn stage

• A history of frequent falls, gait and balance dysfunction and postural instability

• ON-freezing

• Ability to perform a gait/walking task (under close supervision),

• PD participants referred by Dr. Jog to the functional neurosurgeon for SCS implantation for treatment of their gait and balance dysfunction and/or for their freezing of gait.

• SCS eligibility has been confirmed by neurologist and neurosurgeon

• Patients who receive SCS for their gait and mobility must participate in this study in order to determine which SCS parameters provide the patient with the best outcome for their PD symptoms.

• able to give informed consent

• Able to attend all clinic visits and assessments

• No dementia or psychiatric abnormalities on neuropsychological testing

• No significant secondary causes (such as cerebrovascular disease, normal pressure hydrocephalus, peripheral neuropathy, severe degenerative lower limb or back disease).

• we had a few devices to include exploratory trial in atypical PD (MSA, PSP, and CBD confirmed diagnosis from clinic).

Exclusion Criteria:

• History of stroke

• History of ALS or Myasthenia Gravis

• Offending medications (Lithium, valproate, steroids, amiodarone, beta-adrenergic agonists (e.g. salbutamol).

• Persons prescribed zonisamide

• Women reporting that they are pregnant

• Persons medically unstable with contraindications to SCS will be excluded

• Previous brain surgery or cardiac pacemaker

• Eligibility for deep brain stimulation surgery

• Moderately severe parkinsonism in the context of unstable pharmacological treatment

• Dementia as assessed by DSM criteria or severe cognitive disturbances

• Severe psychiatric symptoms (in particular, hallucinations and depression)

• Bad general health

• Lack of compliance at follow-up

• Severe dyskinesias

• Significant cognitive impairment

Related Conditions & MeSH terms

• Atypical Parkinsonism
• Parkinson Disease
• Parkinsonian Disorders

Intervention

Device:
• Spinal cord stimulation
Range of pulse widths (200-500 microseconds) and frequencies (30-130 Hz) will be assessed for each patient

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Western University, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (14)

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. — View Citation

Fénelon 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. — View Citation

Ferraye MU, Debû B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardès S, Pollak P. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease. Brain. 2010 Jan;133(Pt 1):205-14. doi: 10.1093/brain/awp229. Epub 2009 Sep 22. — View Citation

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. Review. — View Citation

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. — View Citation

Giladi N, Horak FB, Hausdorff JM. Classification of gait disturbances: distinguishing between continuous and episodic changes. Mov Disord. 2013 Sep 15;28(11):1469-73. doi: 10.1002/mds.25672. Review. — View Citation

Hassan S, Amer S, Alwaki A, Elborno A. A patient with Parkinson's disease benefits from spinal cord stimulation. J Clin Neurosci. 2013 Aug;20(8):1155-6. doi: 10.1016/j.jocn.2012.08.018. Epub 2013 Feb 26. — View Citation

Jenkinson N, Nandi D, Muthusamy K, Ray NJ, Gregory R, Stein JF, Aziz TZ. Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus. Mov Disord. 2009 Feb 15;24(3):319-28. doi: 10.1002/mds.22189. — View Citation

Landi A, Trezza A, Pirillo D, Vimercati A, Antonini A, Sganzerla EP. Spinal cord stimulation for the treatment of sensory symptoms in advanced Parkinson's disease. Neuromodulation. 2013 May-Jun;16(3):276-9. doi: 10.1111/ner.12005. Epub 2012 Dec 10. — View Citation

Liu HG, Zhang K, Yang AC, Zhang JG. Deep brain stimulation of the subthalamic and pedunculopontine nucleus in a patient with Parkinson's disease. J Korean Neurosurg Soc. 2015 Apr;57(4):303-6. doi: 10.3340/jkns.2015.57.4.303. Epub 2015 Apr 24. — View Citation

Nagatsua T, Sawadab M. L-dopa therapy for Parkinson's disease: past, present, and future. Parkinsonism Relat Disord. 2009 Jan;15 Suppl 1:S3-8. doi: 10.1016/S1353-8020(09)70004-5. Review. — View Citation

Santana MB, Halje P, Simplício 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. — View Citation

Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. Brain. 2007 Jun;130(Pt 6):1596-607. Epub 2007 Jan 24. — View Citation

Yadav AP, Fuentes R, Zhang H, Vinholo T, Wang CH, Freire MA, Nicolelis MA. Chronic spinal cord electrical stimulation protects against 6-hydroxydopamine lesions. Sci Rep. 2014 Jan 23;4:3839. doi: 10.1038/srep03839. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tailored SCS programming	Participants following SCS implantation will undergo 3 programming visits. 9 SCS programs will be tested in a repeated fashion on separate days and at different times of the day (morning vs afternoon). The SCS setting(s) to produce the best motor (gait) response will be used by the participant in-home. SCS device will not be used during this time period.	3 weeks
Primary	Changes in spatiotemporal gait measures using objective gait analysis	Spatiotemporal gait parameters known to be affected in parkinsonian syndromes will be analyzed over a 12 month period using gait analysis software. Best SCS setting tailored to each participant's gait symptoms will be assessed at 3-, 6- and 12-months time-points.	12 months
Secondary	Changes in UPDRS-III scores	UPDRS-III assessment will be assessed pre-surgery and post-surgery at 3-, 6- and 12-month time-points while participants are OFF/ON-dopaminergic medication and OFF/ON SCS.	12 months
Secondary	Changes in NFOG-Q scores	NFOG-Q scores will be assessed pre-surgery and post-surgery at 3-, 6- and 12-month time-points.	12 months
Secondary	Changes in PDQ-39 scores	PDQ-39 scores will be assessed pre-surgery and post-surgery at 3-, 6- and 12-month time-points.	12 months
Secondary	Changes in ABC scores	ABC scores will be assessed pre-surgery and post-surgery at 3-, 6- and 12-month time-points.	12 months
Secondary	Changes in QoL scores	QoL scores will be assessed pre-surgery and post-surgery at 3-, 6- and 12-month time-points.	12 months
Secondary	DaTscan imaging	Asymmetry and specific binding ratios (SBRs) of the striatal regions of dopamine transporter from I-123 FP-CIT SPECT images will be quantitatively analyzed from pre-surgery and 12-months of SCS use.	12-months
Secondary	Proprioception testing	KINARM and lower leg KINARM type of robot collects reaction time, speed, force, accuracy and trajectory using a robotic object hitting game to assess cognitive and motor skills to be conducted pre-surgery, and post-SCS at 3-, 6- and 12-months	12-months