Clinical trial NCT02539784: Thoracic Spinal Cord Stimulation as a Symptomatic Treatment for Advanced Parkinson's Disease
Official title: Thoracic Spinal Cord Stimulation as a Symptomatic Treatment for Advanced Parkinson's Disease: A Phase I Safety and Efficacy Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Parkinson
Keywords: stimulation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-09-03
Enrollment: 6
Sex: ALL
Minimum age (years): 45
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of severe adverse events and adverse events reported
timeFrame: at week 30
Secondary outcomes:
measure: Tolerance and global statement
timeFrame: After surgery (DO), at week 4, 8, 13, 18 and 30
measure: Difference of UPDRS-III scores with and without stimulation in ON or OFF medication state
timeFrame: At W4, W9, W14,W30
measure: Difference of UPDRS-III scores without stimulation and after 4 weeks of continuous stimulation in ON or OFF medication state
timeFrame: At W4, W8, W9, W13, W14,W18
measure: Difference of global UPDRS between screening and others visits, in OFF and ON medication state
timeFrame: At W-4, W8, W13, W18,W30
measure: Difference of Walking Time Measurement scores with and without stimulation in ON or OFF medication state
timeFrame: At W4, W9, W14,W30
measure: Difference of Walking Time Measurement scores without stimulation and after 4 weeks of continuous stimulation in ON or OFF medication state
timeFrame: At W4, W8, W9, W13, W14,W18
measure: Pain assessment using visual pain scale and Saint Antoine Pain Questionnaire
timeFrame: After 4, 9, 13 and 30 weeks after surgery
measure: Paresthesia assessment using visual pain scale and Saint Antoine Pain Questionnaire
timeFrame: After 4, 9, 13 and 30 weeks after surgery
measure: Clinical abnormalities demonstrated during a comprehensive sensitive examination
timeFrame: At W4, W8, W13, W18, W30
measure: Differences of MDRS, LARS, MADRS, PDQ-39 scores between screening and the end of the study
timeFrame: At W-4 and W30
measure: Change of daily L-Dopa equivalent dose
timeFrame: At W4, W8, W13, W18, W30
Other outcomes:
Locations:
city: Creteil
country: France
facility: Henri Mondor Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Claire Thiriez, MD
role: PRINCIPAL_INVESTIGATOR
References: