Comparative Study in Patients With Refractory Chronic Lower Limb Neuropathic Pain and/or Back Neuropathic Pain.

Study Overview
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Brief Summary
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Neuropathic pain is described as a pain initiated or caused by a primary lesion or dysfunction in the nervous system. It is thus often a chronic affection, as a difficult-to-treat condition. As such, there is growing proportion of patients with inefficient pain relief. The prevalence of chronic neuropathic pain has been estimated from 6.9 to 10% in the general population and represents a heavy financial burden for the health care systems. Spinal Cord Stimulation (SCS) is a well-established therapy to alleviate severe intractable neuropathic pain (SCS is a reversible treatment option which leads to improve pain relief and quality of life Using conventional SCS, the prerequisite to target any pain relief is to obtain an appropriate coverage of the painful area with induced paresthesia. Despite its effectiveness, conventional SCS has some limitations (Selectivity, Energy consumption …) and in order to address these limitations and challenges, medical devices and neuromodulation industries have developed the Dorsal Root Ganglion (DRG) stimulation. DRG stimulation appears to be a promising technology that can be proposed to patients with chronic neuropathic pain for several reasons: DRG stimulation has shown promising results in pathologies generating focal pain with more selectively than SCS, lead localization appeared to be less discriminative than SCS. Consequently, DRG seems more stable and efficient to relief pain with lower energy consumption than SCS (therapy can be delivered with very low amplitude compared to SCS). Last but not least, Abbott technology has moved forward to Burst stimulation a couple of years ago and validated this new way of delivering electrical stimulation through several major publications. To our knowledge, applying new waveforms to DRG has not been yet validated. This will represent a fantastic opportunity to refine the design of the next generation of Internal Pulse Generators (IPGs). To date, the baseline study comparing DRG stimulation to SCS is the ACCURATE study. This is a high quality prospective, multicenter, randomized comparative trial conducted in 152 patients implanted with either SCS or DRG stimulation system. Although ACCURATE study is well designed, it has some limitations. To bridge this gap, the investigators propose to conduct a randomized controlled trial (RCT) with a crossover design, where SCS and DRG stimulation will be used within patient in three conditions: (i) SCS alone, (ii) DRG stimulation alone (DRGS), (iii) combination of SCS and DRGS (DUAL). Our goal will be to compare SCS vs DRGS vs DUAL therapies in order to establish the superiority of DRG stimulation over SCS in a crossover design, assess the added value of hybrid stimulation (DUAL) over the separate standalone stimulation types, compare the different cortical pathways involved in both techniques, by functional imaging, incl. MRI, analyze energy consumption by optimizing neural targeting. assess the added value of applying Burst on these different targets, after a 3-month follow-up and to reinforce the perception of neurostimulation techniques through the pain community, as the investigators will demonstrate their benefits on pain relief, functional capacity and quality of life, with objectives measures and a randomized design. This study represents a unique opportunity to boost the rationale of SCS/DRGS since each arm of treatment will be blinded for the patient and the implanter.

Official Title
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Prospective, Randomized, Double Blinded Crossover Study Comparing Spinal Cord Stimulation (SCS) vs Dorsal Root Ganglion Stimulation (DRGS) vs Association of Both (DUAL) in Patients With Refractory Chronic Lower Limb Neuropathic Pain and/or Back Neuropathic Pain

Conditions
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Pain, Neuropathic

Intervention / Treatment
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* Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has ≥ 18 years and ≤ 80 years Subject has a VAS ≥ 5 Subject has refractory chronic lower limbs neuropathic pain (e.g. diabetic foot peripheral neuropathy, foot peripheral neuropathy, ankle peripheral neuropathy) or/and neuropathic back pain for at least 6 months Subject has stable pain for at least 30 days Pain medication(s) dosage(s) is/are stable for at least 30 days Subject is refractory to other treatment modalities (e.g. Medication, psychological therapies, pain interventions, surgery) Subject is eligible for SCS after a pre-implantation assessment by a multidisciplinary team, as described by the French National Authority for Health Subject understands and accepts constraints of the study. Patient covered by French national health insurance. Subject has given written consent to the study after having received clear and complete information Non inclusion criteria: Subject has a coagulation disorder Subject is or has been treated with SCS, subcutaneous or peripheral nerve stimulation, an intrathecal drug delivery system Subject has had corticosteroid therapy within the past 30 days Subject has had radiofrequency therapy within the past 3 months Subject has been diagnosed with cancer in the past 2 years Subject has had a spinal surgery within the past 6 months Subjects requiring closer protection, i.e. minors, pregnant women, nursing mothers, subjects deprived of their freedom by a court or administrative decision, subjects admitted to a health or social welfare establishment, major subjects under legal protection, and finally patients in an emergency setting Simultaneous participation to any interventional study on health product or any study able to interfere with the current study endpoints. Pregnant or breastfeeding women, women at age to procreate and not using effective contraception Brain MRI contraindication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Screening
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SCS/ DRGS/DUAL /Dual*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|
| Active Comparator: SCS/DUAL/DRGS/DRGS*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|
| Active Comparator: DRGS/SCS/DUAL/DUAL*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|
| Active Comparator: DRGS/DUAL/SCS/SCS*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|
| Active Comparator: Dual/DRGS/SCS/SCS*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|
| Active Comparator: Dual/SCS/DRGS/DRGS*<br> | Other: Spinal Cord Stimulation, association of both (DUAL), Dorsal Root Ganglion stimulation<br>* Lead Implantation which will be conducted in 2 steps: Lead implantation: 8-contact SCS percutaneous lead on SC and 8-contact lead on DRG. Neurostimulation trial phase (Mode DUAL). IPG implantation + Randomization + 1st leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 2nd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). 3rd leads programming (SC, DRG or DUAL stimulation according to randomization sequence). All patients will be switched to Burst waveform for a 1- month follow-up period while keeping the last allocated stimulation type in the randomized crossover arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare pain relief with SCS vs DRGS vs association of both (DUAL) in patients with chronic lower limb neuropathic pain and/or back neuropathic pain following each stimulation modality within a 3-month crossover period. | Proportion of patients having a reduction of 50% on the Visual Analogic Scale (VAS) score (0-No pain/10-worst pain imaginable) (assessed with a 5-day pain diary) between baseline (before leads implantation) and after the end of each period of crossover phase. | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pain intensity score | Pain intensity will be assessed using the Visual Analogic Scale (VAS) score (0-No pain/10-worst pain imaginable) at Lead Implantation Visit, M0, M1, M2, M3, M4, M6 and M12. | 12 months | 
| Mean pain surface (cm²) | Global Pain surface (cm²) measured using a pain mapping tool at Lead Implantation Visit, M0, M1, M2, M3, M4, M6 and M12. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dorsal Root Ganglion, Spinal Cord Stimulation