Title: Multicentre, Double Blind, Randomized Controlled Trial of 10kHz High-Frequency Spinal Cord Stimulation for Chronic Neuropathic Low Back Pain (MODULATE-LBP)
Funder: Department of Health and Social Care

Abstract: Introduction: Many patients with Chronic Neuropathic Lower Back Pain (CNLBP) have a significant neuropathic component(6-9). This is associated with greater pain intensity, disability and is commonly refractory to medical and surgical intervention. Given the prevalence and burden of intractable CNLBP, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10kHz (10kHz-SCS) provides pain relief without the paraesthesias typical of conventional low-frequency SCS. A single-arm cohort study of 20 CNLBP patients without previous spine surgery demonstrated that the use of 10kHz-SCS was associated with significant improvements in pain, disability and quality of life (5). This was sustained for 12 months and ongoing follow up has shown similar improvements at 3 years (13). Aim: The objective of this study is to evaluate the efficacy, safety and cost-effectiveness of 10 kHz-SCS in the treatment of CNLBP patients without prior spinal surgery. Materials and Methods: Study Design and Population Multicentre, randomised, blinded, superiority, sham-controlled trial with parallel economic evaluation. Patients will be individually allocated to activated 10kHz-SCS plus usual care (intervention) or sham 10kHz SCS plus usual care (control) and followed up to 6 months.Consenting patients already under the care of the study investigators will be assessed for eligibility based on inclusion and exclusion criteria and randomized across 2 pain Neuromodulation centres in England.Subjects with intractable CNLBP refractory to conservative therapy without prior spine surgery for a minimum of 6 months will be recruited. Randomization and Blinding Patients will be allocated 1:1 to intervention or control stratified by centre using web-based randomisation to ensure concealment . Patients, clinicians, outcome assessors and analysts will be all blinded. Sample Size For our primary outcome of pain severity VAS (0-100mm), IMMPACT (Initiative on Methods, Measurement and Pain Assessment on Clinical Trials) propose a minimally important clinical difference (MICD) of 20mm. To detect this MICD and based on a back/leg pain VAS standard deviation of 25mm as seen in previous conventional and 10kHz-SCS RCTs, at 90% power and 5% alpha, and a worst case attrition rate of 30% at 6-months follow up. We will require a total of 48 participants recruited per group with a 1:1 allocation. Interventions Both intervention and control will receive an implant of 10kHz-SCS device. This will consist of two Octapolar leads connected to an implanted pulse generator (IPG) sited in the subcutaneous tissue of the buttock or flank. The first of the two leads will be implanted via an epidural puncture so that the lead overlies the T9/10 disc space and will be fitted in port one of the IPG. The second lead will be implanted subcutaneously behind the IPG and will serve to dissipate the current from the battery in the sham participants and will be fitted in port two of the IPG. The potential benefits to patients and the NHS The proposed research will be the first double-blind randomized placebo-controlled trial examining the efficacy of 10kHz-SCS in the management of CNLBP (and one of the first double blind RCTs of SCS). This study design provides the highest level of evidence for pain treatments. If the therapy provides superior patient outcomes, over placebo, and is cost-effective this study will provide key evidence for NICE and local commissioners and will inform funding and availability of SCS to this population. The study provides the opportunity to demonstrate the role of 10 kHz SCS as an alternative to lumbosacral spine surgery and thus avoid the need for an expensive and non-reversible therapy. Furthermore, a proportion of surgical patients will go onto develop &ldquo;Failed back surgery syndrome&rdquo; i.e. continue to suffer pain despite back surgery, a difficult and expensive condition to treat.

Lay abstract: Among patients with long-term low back pain; one in eight may have nerve pain, or &ldquo;neuropathic pain.&rdquo; Neuropathic pain is associated with greater pain severity and worse health-related quality of life. If surgery is not possible, few treatment options are available. Spinal cord stimulation (SCS) involves implanting a medical wire through a needle puncture adjacent to the spinal cord. The wire is connected to a battery implanted under the skin of the buttock or abdomen. The battery sends a current that creates an electrical field that can be detected by the patient and can limit pain messages. SCS is a well-established effective treatment of unresponsive nerve pain, however its usefulness in back pain is limited. A new form of SCS known as 10kHz spinal cord stimulation (10kHz-SCS) includes a non-detectable (by the subject) electrical field that has shown effectiveness in the treatment of low back pain after back surgery in a number of studies. We conducted an uncontrolled pilot study of 10kHz-SCS in 21 neuropathic low back pain patients with no previous back surgery and showed important improvements in pain and functioning, reduction in pain medication use, and 75% return to work. Given the encouraging results of our pilot study we now propose a full clinical trial to definitively test this therapy. We will implant all patients with 2 stimulator wires with a battery. Half will be randomly assigned to active stimulation whilst the remainder will get sham therapy (device implanted but correct stimulation not activated) for 6 months. As the device generates no sensations, neither patient, nor study personnel will be aware of treatment allocation so that results of study are not subject to placebo effect bias. We will assess pain severity, disability, emotional distress, health-related quality of life, and return to work at one, three, and six months.

Research activity codes: 6.7 PHYSICAL
Health categories: NEUROLOGICAL