JPR_A_460563 2891..2901

Journal of Pain Research Dovepress

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 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.

Study Goals and Objectives

The primary objective of this study is to document the comparative effectiveness and safety of peripheral nerve stimulation (PNS) plus conventional medical management (CMM) versus CMM alone, in the treatment of chronic, intractable peripheral neuropathic pain. The secondary objectives are to:

  1. Evaluate the comfort, subject compliance, and usability of the wearable components of the Nalu Neurostimulation system.
  2. Evaluate subject satisfaction and response to the system with patient reported outcomes (PRO).

Participants

Subjects with peripheral neuropathic pain in the knee, low back, shoulder or foot/ankle, and who have not obtained satisfactory results with CMM will be candidates for study participation. Once informed consent is obtained, subjects will move into the screening phase of the study, which will include a baseline evaluation to ensure inclusion/exclusion criteria are met.

Inclusion Criteria

  1. Subject is between 18 and 80 years of age at the time of enrollment.
  2. Subject would have been prescribed PNS therapy regardless of participation in this study.
  3. Subject has chronic (defined as at least 6-month duration), intractable peripheral neuropathic pain, exclusive of the craniofacial region.
  4. Subject should have a pain score of at least 6, in the target area of pain, as recorded on the BPI-Q5 (NRS) at screening.
  5. Subject is willing to cooperate with the study requirements including compliance with the study procedures.

Exclusion Criteria

  1. Subject currently has an active implantable medical device such as a drug pump.
  2. Subject has previously failed PNS, SCS, or Dorsal Root Ganglion (DRG) therapy.
  3. Pain is completely absent at rest.
  4. Subject has clinical evidence of complex regional pain syndrome (CRPS).
  5. Subject has an active malignant neoplasm or evidence of paraneoplastic syndrome.

Study Design

The study is a prospective, multicenter RCT evaluating the comparative effectiveness and safety of PNS plus CMM versus CMM alone. Up to 100 subjects will be randomized 2:1 (PNS+CMM to CMM) at up to 20 centers in the United States (US). The total follow-up period is 36 months, following implant, for all participants.

Primary Effectiveness Hypothesis

The primary effectiveness hypothesis for this study is based upon the responder rate, defined as percent of subjects with ≥50% reduction in NRS for their primary area of pain, captured on the Brief Pain Inventory-Question 5 (BPI-Q5).

Conclusion

This study will provide significant data on the long-term efficacy and safety of the Nalu Neurostimulation System for patients suffering from chronic pain due to peripheral neuropathy.