Thoracic Spinal Cord Stimulation as a Symptomatic Treatment for Advanced Parkinson's Disease

Study Overview
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Brief Summary
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Following the so call honey moon period, motor symptoms of Parkinson's Disease (PD) become difficult to control with dopaminergic treatments alone. Deep brain stimulation (DBS) of the subthalamic nucleus and internal globus pallidus helps to treat fluctuating parkinsonian patients restoring a decent quality of life. However, DBS need a long, complex and invasive surgery to succeed. Thus, there is a critical need to develop alternative treatments, more accessible and less invasive. Thoracic posterior spinal cord stimulation has been used for decades to treat chronic neuropathic pains. Safety and efficacy have already been demonstrated in neuropathic pain. Experimentally, SCS has also demonstrated to improve locomotor activity in two different rodents' models of parkinson's disease. The purpose of this study is to determine whether thoracic SCS is safe and could induce a benefit motor parkinsonian symptoms without any impact on cognitive function and axial disability.

Detailed Description
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The present pilot study will enroll 6 patients suffering from advanced Parkinson Disease (PD). Investigator will assess the safety, tolerance and efficacy of Spinal Cord Stimulation (SCS) with frequencies of 50, 100 and 130 Hz in a shuffle randomized for each patient. Briefly, each frequency will be evaluated immediately after and 4 weeks following SCS initiation with UPDRS-III, pain scales, and Hauser's diary. The best frequency for each patient will be then selected and maintained activated for 12 additional weeks. At the end of these 12 weeks, new assessment including UPDRS, visual pain scale, SAINT-ANTOINE Pain Questionary, PDQ-39 (quality of life), daily L-dopa equivalent dose, MDRS (cognitive status), LARS (apathy status) and MADRS (depression status) will be compared to the inclusion data of each patient. Primary endpoints include the safety of thoracic SCS by collected the number of adverse event and the efficacy by measuring the UPDRS-III OFF med/ON stim at 30 weeks.

Official Title
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Thoracic Spinal Cord Stimulation as a Symptomatic Treatment for Advanced Parkinson's Disease: A Phase I Safety and Efficacy Study

Conditions
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Parkinson

Intervention / Treatment
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* Device: Kit for Spinal Cord Stimulator System  SCS Systems  : PRECISION® System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient from 45 to 69 years old Affiliated to the French social health care system Menopausal or under contraception for women Parkinson's disease according to UK PDSBB's criteria with diagnosis for ≥ 5 years OFF UPDRS-III ≥ 25 Acute dopa-response ≥ 50% for UPDRS-III in an L-Dopa challenge Fluctuations with periods off ≥ 25% of the time of awakening or dyskinesia ≥ 25% 3≤ Hoehn & Yahr ≤ 4 No change in anti-parkinsonian drugs in the last month Informed consent signed for the study Exclusion Criteria: Patients major protected Pregnancy Deep brain stimulation or other neurosurgical treatment MDRS Score < 130 or depression scale MADRS ≥ 20 Respiratory insufficiency (surgery belly decubitus) Abnormalities on brain MRI which evoke a secondary parkinsonian syndrome Spinal cord's injury on MRI or posterior cordonal's pathology on sensitive evoked potential Neuropathy on EMG Prior spinal surgery and spinal pathology at the dorsal level Patients having already been included in therapeutic studies Patient with a cardiac pacemaker, a defibrillator or any other implanted active pacemaker Patient requiring diathermy process Patient having a pathology requiring an MRI follow-up care

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 69 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spinal Cord Stimulation<br> | Device: Kit for Spinal Cord Stimulator System  SCS Systems  : PRECISION® System<br>* 3 frequencies of SCS are tested for each patient : 50, 100 and 130 Hz<br>* Other names: Boston Scientific Device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of severe adverse events and adverse events reported |  | at week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance and global statement | Clinical assessment | After surgery (DO), at week 4, 8, 13, 18 and 30 | 
| Difference of UPDRS-III scores with and without stimulation in ON or OFF medication state |  | At W4, W9, W14,W30 | 
| Difference of UPDRS-III scores without stimulation and after 4 weeks of continuous stimulation in ON or OFF medication state |  | At W4, W8, W9, W13, W14,W18 | 
| Difference of global UPDRS between screening and others visits, in OFF and ON medication state |  | At W-4, W8, W13, W18,W30 | 
| Difference of Walking Time Measurement scores with and without stimulation in ON or OFF medication state |  | At W4, W9, W14,W30 | 
| Difference of Walking Time Measurement scores without stimulation and after 4 weeks of continuous stimulation in ON or OFF medication state |  | At W4, W8, W9, W13, W14,W18 | 
| Pain assessment using visual pain scale and Saint Antoine Pain Questionnaire |  | After 4, 9, 13 and 30 weeks after surgery | 
| Paresthesia assessment using visual pain scale and Saint Antoine Pain Questionnaire |  | After 4, 9, 13 and 30 weeks after surgery | 
| Clinical abnormalities demonstrated during a comprehensive sensitive examination |  | At W4, W8, W13, W18, W30 | 
| Differences of MDRS, LARS, MADRS, PDQ-39 scores between screening and the end of the study |  | At W-4 and W30 | 
| Change of daily L-Dopa equivalent dose |  | At W4, W8, W13, W18, W30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stimulation