Clinical trial NCT03526991: Exploring the Effects of Spinal Cord Stimulation in Parkinson's Disease.
Official title: Exploring the Effects of Spinal Cord Stimulation in Parkinson's Disease.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Freezing of Gait
Locomotion
Spinal cord stimulation
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2018-05-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A total of 10 patients with a diagnosis of Parkinson's disease and treatment refractory freezing of gait will be recruited in this study.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: Parkinson Disease (PD) patients experience a variety of motor issues such as walking difficulties, loss of balance, and freezing while walking, which impacts their quality of life. Some symptoms, like freezing of gait (FOG), do not respond to medications typically used to treat PD. Current surgical procedures used to alleviate PD symptoms also do not always improve FOG. Since many traditional therapies have failed for the treatment of FOG, researchers have proposed the use of newer treatments. Recent research in animal models and clinical human data using SCS has produced promising results, specifically showing improvement in FOG with the use of SCS in patients with PD.

The purpose of this study is to evaluate the effectiveness of spinal cord stimulation (SCS) for the management of freezing of gait (FOG) that does not respond to conventional treatments in subjects with Parkinson's disease (PD). The investigators hypothesize that SCS significantly decreases FOG episodes in patients with PD.

1. Assess the safety, tolerability and preliminary evidence of effectiveness of upper thoracic spinal cord stimulation for freezing of gait in Parkinson's (PD) patients.
2. Explore the effects of two SCS programming paradigms on motor, nonmotor and quality of life measures in PD patients with freezing of gait.

Detailed description: Freezing of gait (FOG) is a devastating motor phenomenon which may occur in patients with Parkinson's Disease (PD) and other neurodegenerative disorders. It is characterized by episodes during which patients cannot generate effective forward stepping movements in the absence of motor deficits.

FOG leads to reduced mobility, loss of independence, social embarrassment, and caregiver stress. While most motor features of PD respond robustly to dopaminergic agents and deep brain stimulation (DBS), there are currently no effective treatments for FOG.

Indirect evidence from case reports of PD patients undergoing spinal cord stimulation (SCS) for neuropathic pain, has consistently described a positive effect of SCS on FOG. In addition, two recent reports demonstrated that thoracic SCS improved locomotion and FOG in patients with advanced PD. The promising role of SCS for the treatment of FOG in PD has encouraged us to assemble a multi-disciplinary team for the systematic investigation of the motor effects of SCS on FOG, locomotion and other parkinsonian features.

The current study integrates minimally invasive SCS and the use of robotic technology to determine objective gait parameters. The investigators propose a pilot study for the implantation of SCS to the spinal cord on PD patients with treatment-refractory FOG, including a longitudinal assessment of motor outcomes. Motors assessments will include: PAMSys and LEGSys to characterize gait, ActivePERS motion sensor to monitor ambulation parameters and overall activity at home, participants will also be given electronic tablets for the ActivePERS to collect real time information about falls.

Eligibility criteria: Inclusion Criteria:

* Males and females between older than 18 years of age.
* Able to provide informed consent
* Diagnosed with idiopathic PD (meeting at least two of the three United Kingdom (UK) Brain Bank criteria for PD, specifically bradykinesia plus resting tremor or rigidity) whose major complaints is levodopa refractory FOG. Levodopa refractoriness will be defined as lack of subjective improvement on FOG episodes as reported by the patient.
* Documented dopaminergic response
* Optimized PD treatment including dopaminergic medications, and/or deep brain stimulation (DBS) therapy
* Presence of at least two self-reported levodopa refractory episodes of FOG per day, not limited to start hesitation
* At least one witnessed freezing event during the screening visit in the 'on' medication state (defined as 45 minutes after a regular dose of Levodopa for the subject being studied)

Exclusion Criteria:

Presence of any co-morbid psychiatric illness(es) that would interfere with the completion of the study or pose risk to the patient, as defined below:

* Presence of psychosis
* Depression BDI \>14
* Anxiety BAI \>14

  * Presence of an active infection, uncontrolled diabetes mellitus, immunosuppression or other medical contraindications to undergoing SCS implantation
  * Patients who are currently on anticoagulation treatment or unable to hold off the anticoagulants (including Plavix, Aspirin, Warfarin, etc.) 7 days prior to the SCS procedure.
  * Moderate Cognitive Impairment defined by a MoCA \< 23
  * Diagnosis of failed back surgery syndrome, Complex Regional Pain Syndrome (CRPS) or intractable low back pain and leg pain.
  * Women of childbearing potential will be excluded as from participation due to the limited safety data of thoracic SCS on the fetus.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 12-months
Secondary outcomes:
measure: Change in New Freezing of Gait Questionnaire (NFOG-Q) score
timeFrame: Baseline (pre-surgery), and over a 12month follow up period
measure: 10-meter walk
timeFrame: Baseline (pre-surgery), and over a 12-month follow up period
measure: Montreal Cognitive Assessment (MoCA),
timeFrame: Baseline (pre-surgery), and over a 12month follow up period
measure: Change in MDS-UPDRS score
timeFrame: Baseline (pre-surgery), and over a 12month follow up period
measure: Non-Motor Symptoms Scale (NMSS)
timeFrame: Baseline (pre-surgery), and over a 12month follow up period
measure: Parkinson's Disease Questionnaire (PDQ39)
timeFrame: Baseline (pre-surgery), and over a 12month follow up period
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Nora Vanegas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giladi N, Kao R, Fahn S. Freezing phenomenon in patients with parkinsonian syndromes. Mov Disord. 1997 May;12(3):302-5. doi: 10.1002/mds.870120307.
citation: Schoneburg B, Mancini M, Horak F, Nutt JG. Framework for understanding balance dysfunction in Parkinson's disease. Mov Disord. 2013 Sep 15;28(11):1474-82. doi: 10.1002/mds.25613. Epub 2013 Aug 7.
citation: Espay AJ, Fasano A, van Nuenen BF, Payne MM, Snijders AH, Bloem BR. "On" state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication. Neurology. 2012 Feb 14;78(7):454-7. doi: 10.1212/WNL.0b013e3182477ec0. Epub 2012 Jan 18.
citation: Fasano A, Lozano AM. Deep brain stimulation for movement disorders: 2015 and beyond. Curr Opin Neurol. 2015 Aug;28(4):423-36. doi: 10.1097/WCO.0000000000000226.
citation: 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.
citation: Soltani F, Lalkhen A. Improvement of Parkinsonian Symptoms With Spinal Cord Stimulation: Consequence or Coincidence? J Neurol Neurosurg Psychiatry. 2013;84(11):e2.74-e2. doi:10.1136/jnnp-2013-306573.165.
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.
citation: 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.
citation: Rohani M, Kalsi-Ryan S, Lozano AM, Fasano A. Spinal cord stimulation in primary progressive freezing of gait. Mov Disord. 2017 Sep;32(9):1336-1337. doi: 10.1002/mds.27103. Epub 2017 Jul 6. No abstract available.
citation: Giladi N, Tal J, Azulay T, Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe WH, Stocchi F, Tolosa E. Validation of the freezing of gait questionnaire in patients with Parkinson's disease. Mov Disord. 2009 Apr 15;24(5):655-61. doi: 10.1002/mds.21745.
citation: de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. doi: 10.1016/S1474-4422(06)70471-9.
citation: Shulman JM, De Jager PL, Feany MB. Parkinson's disease: genetics and pathogenesis. Annu Rev Pathol. 2011;6:193-222. doi: 10.1146/annurev-pathol-011110-130242.
citation: Turner BM, Forstmann BU, Love BC, Palmeri TJ, Van Maanen L. Approaches to Analysis in Model-based Cognitive Neuroscience. J Math Psychol. 2017 Feb;76(B):65-79. doi: 10.1016/j.jmp.2016.01.001. Epub 2016 Feb 17.
citation: Snijders AH, Takakusaki K, Debu B, Lozano AM, Krishna V, Fasano A, Aziz TZ, Papa SM, Factor SA, Hallett M. Physiology of freezing of gait. Ann Neurol. 2016 Nov;80(5):644-659. doi: 10.1002/ana.24778. Epub 2016 Oct 7.
citation: Fleury V, Pollak P, Gere J, Tommasi G, Romito L, Combescure C, Bardinet E, Chabardes S, Momjian S, Krainik A, Burkhard P, Yelnik J, Krack P. Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait. Mov Disord. 2016 Sep;31(9):1389-97. doi: 10.1002/mds.26545. Epub 2016 Feb 17.
citation: Adams C, Keep M, Martin K, McVicker J, Kumar R. Acute induction of levodopa-resistant freezing of gait upon subthalamic nucleus electrode implantation. Parkinsonism Relat Disord. 2011 Jul;17(6):488-90. doi: 10.1016/j.parkreldis.2011.02.014. Epub 2011 Mar 11. No abstract available.
citation: van Nuenen BF, Esselink RA, Munneke M, Speelman JD, van Laar T, Bloem BR. Postoperative gait deterioration after bilateral subthalamic nucleus stimulation in Parkinson's disease. Mov Disord. 2008 Dec 15;23(16):2404-6. doi: 10.1002/mds.21986.
citation: Rocchi L, Carlson-Kuhta P, Chiari L, Burchiel KJ, Hogarth P, Horak FB. Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease: laboratory investigation. J Neurosurg. 2012 Dec;117(6):1141-9. doi: 10.3171/2012.8.JNS112006. Epub 2012 Oct 5.
citation: Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes 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.
citation: Thevathasan W, Cole MH, Graepel CL, Hyam JA, Jenkinson N, Brittain JS, Coyne TJ, Silburn PA, Aziz TZ, Kerr G, Brown P. A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. Brain. 2012 May;135(Pt 5):1446-54. doi: 10.1093/brain/aws039. Epub 2012 Mar 6.
citation: Zrinzo L, Zrinzo LV, Hariz M. The peripeduncular nucleus: a novel target for deep brain stimulation? Neuroreport. 2007 Aug 6;18(12):1301-2. doi: 10.1097/WNR.0b013e3282638603.
citation: Thevathasan W, Coyne TJ, Hyam JA, Kerr G, Jenkinson N, Aziz TZ, Silburn PA. Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease. Neurosurgery. 2011 Dec;69(6):1248-53; discussion 1254. doi: 10.1227/NEU.0b013e31822b6f71.
citation: Compton AK, Shah B, Hayek SM. Spinal cord stimulation: a review. Curr Pain Headache Rep. 2012 Feb;16(1):35-42. doi: 10.1007/s11916-011-0238-7.
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.
citation: Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg. 1967 Jul-Aug;46(4):489-91. No abstract available.
citation: Cook AW, Weinstein SP. Chronic dorsal column stimulation in multiple sclerosis. Preliminary report. N Y State J Med. 1973 Dec 15;73(24):2868-72. No abstract available.
citation: Thiriez C, Gurruchaga JM, Goujon C, Fenelon G, Palfi S. Spinal stimulation for movement disorders. Neurotherapeutics. 2014 Jul;11(3):543-52. doi: 10.1007/s13311-014-0291-0.
citation: 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.
citation: 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.
citation: 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.
citation: Kiriakopoulos ET, Tasker RR, Nicosia S, Wood ML, Mikulis DJ. Functional magnetic resonance imaging: a potential tool for the evaluation of spinal cord stimulation: technical case report. Neurosurgery. 1997 Aug;41(2):501-4. doi: 10.1097/00006123-199708000-00042.
citation: Holsheimer J. Which Neuronal Elements are Activated Directly by Spinal Cord Stimulation. Neuromodulation. 2002 Jan;5(1):25-31. doi: 10.1046/j.1525-1403.2002._2005.x.
citation: Weise D, Winkler D, Meixensberger J, Classen J. Effects of spinal cord stimulation in a patient with Parkinson's disease and chronic back pain. J Neurol. 2010;257:S217.
citation: Yadav AP, Nicolelis MAL. Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease. Mov Disord. 2017 Jun;32(6):820-832. doi: 10.1002/mds.27033. Epub 2017 May 12.
citation: Gazelka HM, Freeman ED, Hooten WM, Eldrige JS, Hoelzer BC, Mauck WD, Moeschler SM, Pingree MJ, Rho RH, Lamer TJ. Incidence of clinically significant percutaneous spinal cord stimulator lead migration. Neuromodulation. 2015 Feb;18(2):123-5; discussion 125. doi: 10.1111/ner.12184. Epub 2014 May 5.
citation: Hoelzer BC, Bendel MA, Deer TR, Eldrige JS, Walega DR, Wang Z, Costandi S, Azer G, Qu W, Falowski SM, Neuman SA, Moeschler SM, Wassef C, Kim C, Niazi T, Saifullah T, Yee B, Kim C, Oryhan CL, Rosenow JM, Warren DT, Lerman I, Mora R, Hayek SM, Hanes M, Simopoulos T, Sharma S, Gilligan C, Grace W, Ade T, Mekhail NA, Hunter JP, Choi D, Choi DY. Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter Retrospective Study. Neuromodulation. 2017 Aug;20(6):558-562. doi: 10.1111/ner.12609. Epub 2017 May 11.
citation: Mekhail NA, Mathews M, Nageeb F, Guirguis M, Mekhail MN, Cheng J. Retrospective review of 707 cases of spinal cord stimulation: indications and complications. Pain Pract. 2011 Mar-Apr;11(2):148-53. doi: 10.1111/j.1533-2500.2010.00407.x. Epub 2010 Sep 8.
citation: Engle MP, Vinh BP, Harun N, Koyyalagunta D. Infectious complications related to intrathecal drug delivery system and spinal cord stimulator system implantations at a comprehensive cancer pain center. Pain Physician. 2013 May-Jun;16(3):251-7.
citation: Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. Pain. 2004 Mar;108(1-2):137-47. doi: 10.1016/j.pain.2003.12.016.
citation: Minto S, Zanotto D, Boggs EM, Rosati G, Agrawal SK. Validation of a Footwear-Based Gait Analysis System With Action-Related Feedback. IEEE Trans Neural Syst Rehabil Eng. 2016 Sep;24(9):971-980. doi: 10.1109/TNSRE.2015.2498287. Epub 2015 Nov 5.
citation: Nieuwboer A, Rochester L, Herman T, Vandenberghe W, Emil GE, Thomaes T, Giladi N. Reliability of the new freezing of gait questionnaire: agreement between patients with Parkinson's disease and their carers. Gait Posture. 2009 Nov;30(4):459-63. doi: 10.1016/j.gaitpost.2009.07.108. Epub 2009 Aug 5.