Clinical study of a micro-implantable pulse generator for the treatment of peripheral neuropathic pain: 3-month and 6-month results from the COMFORT-randomised controlled trial.

BACKGROUND: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG). METHODS: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle. RESULTS: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable. CONCLUSIONS: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

Design of a Multicenter, Randomized Controlled Trial for the Treatment of Peripheral Neuropathic Pain (COMFORT Study) with a Micro-Implantable Pulse Generator.

Background: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.

Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm³ in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (<1.5 cm³ in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months.

Understanding whether chronic lower back pain patients with lumbar spinal stenosis benefit from multiple epidural steroid injections prior to the mild® Procedure.

Originally published in Pain Management, this article is a summary of a study performed to look at the benefit, if any, of more than one epidural steroid injection in the spine before the mild® Procedure. Minimally invasive lumbar decompression (commonly known as the mild Procedure) and epidural steroid injections are both common treatment options for lumbar spinal stenosis (commonly referred to as LSS), a condition that causes chronic lower back pain in older adults. To determine how to best treat LSS patients, healthcare professionals use a guide to help with the decision-making process (called an algorithm) to pass through non-medical to more invasive therapies that often includes one or more epidural steroid injections. An epidural steroid injection is medication inserted in the lower back to reduce swelling and provide relief from pain. Researchers wanted to look at a change to when in the treatment process the mild Procedure is carried out. In the study, researchers compared the medical records of participants who had received either just one or no steroid injection prior to the mild Procedure, to participants who received two or more epidural steroid injections prior to the mild Procedure. Similar outcomes in both treatment groups in this study proved that giving more than one epidural steroid injection prior to the mild Procedure did not improve how well patients did and may have delayed patient care. Based on the results of the study, it is recommended that the standard treatment process for LSS patients be changed to give the mild Procedure either as soon as LSS is diagnosed or after the failure of the first epidural steroid injection.

Minimally invasive direct decompression for lumbar spinal stenosis: impact of multiple prior epidural steroid injections.

Background: A modified algorithm for the treatment of lumbar spinal stenosis with hypertrophic ligamentum flavum using minimally-invasive lumbar decompression (mild®)was assessed, with a focus on earlier intervention. Patients & methods: Records of 145 patients treated with mild after receiving 0-1 epidural steroid injections (ESIs) or 2+ ESIs were retrospectively reviewed. Pain assessments as measured by visual analog scale (VAS) scores were recorded at baseline and 1-week and 3-month follow-ups. Results: Improvements in VAS scores at follow-ups compared with baseline were significant in both groups. No statistically significant differences were found between the two groups. Conclusion: Multiple ESIs prior to mild showed no benefit. A modified algorithm to perform mild immediately upon diagnosis or after the failure of the first ESI is recommended.

Lay abstract Physicians use a structured decision-making process (an algorithm) to decide how best to treat lumbar spinal stenosis (LSS) that results from abnormal thickening of the spinal ligaments that run the length of the spinal cord. Early treatments can include one or more epidural steroid injections (ESIs). This study evaluated a change to the algorithm that involves earlier intervention with a minimally invasive, short outpatient procedure that removes a major root cause of the abnormal thickening (lumbar decompression) and leaves no implants behind. Records of patients treated with minimally-invasive lumbar decompression (mild^®) after receiving either a single ESI procedure or none at all, were compared with the records of patients who underwent the mild procedure after receiving two or more ESIs (145 total patients). The patients' pain scores before surgery, at 1 week postsurgery and at 3 months postsurgery were reviewed. The improvements in pain scores following the mild procedure were compared within each group and between the two groups. The improvements in pain scores at both the 1-week and 3-month follow-up visits indicated that the mild procedure had a positive effect for both groups. Further, there were no significant differences in how much pain scores improved when the two groups were compared. Since neither group experienced significantly more pain relief than the other, there appears to be no benefit to having multiple ESI procedures before undergoing the mild procedure. The authors recommend that the algorithm be modified to perform the mild procedure either as soon as LSS is diagnosed or after the failure of the first ESI procedure.