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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
  1. John Hatheway1,
  2. Alexander Hersel2,
  3. Jonathan Song3,
  4. Mitchell Engle4,
  5. Genaro Gutierrez5,
  6. Vishal Khemlani6,
  7. Leonardo Kapural7,
  8. Gregory Moore8,
  9. Reginald Ajakwe9,
  10. Drew Trainor10,
  11. Jennifer Hah11,
  12. Peter S Staats12,
  13. Paul Lynch13,
  14. James Makous14,
  15. Gary Heit15,
  16. Shilpa Kottalgi16 and
  17. Mehul J Desai17
  1. 1Northwest Pain Care, Spokane, Washington, USA
  2. 2Pain Management and Injury Relief, Thousand Oaks, California, USA
  3. 3Arizona Pain Specialists, Scottsdale, Arizona, USA
  4. 4Institute of Precision Pain Medicine, Corpus Christi, Texas, USA
  5. 5Pain Specialists of America, Austin, Texas, USA
  6. 6Columbia Pain Management, Portland, Oregon, USA
  7. 7Center for Clinical Research, Carolinas Pain Institute, Winston-Salem, North Carolina, USA
  8. 8Pacific Sports and Spine, Eugene, Oregon, USA
  9. 9Comprehensive Spine & Pain Physicians, Burbank, California, USA
  10. 10Denver Spine and Pain Institute, Denver, Colorado, USA
  11. 11Division of Pain Medicine, Stanford University, Palo Alto, California, USA
  12. 12Premier Pain Ctr, Shrewsbury, New Jersey, USA
  13. 13US Pain Care, Scottsdale, Arizona, USA
  14. 14Makous Research, LLC, Carlsbad, California, USA
  15. 15Hue University of Medicine and Pharmacy, Hue, Thua Thien Hue, Viet Nam
  16. 16Nalu Medical Inc, Carlsbad, California, USA
  17. 17International Spine, Pain & Performance Center, Washington, District of Columbia, USA
  1. Correspondence to Shilpa Kottalgi, Nalu Medical Inc, Carlsbad CA 92008, California, USA; skottalgi{at}


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.

  • Neuralgia
  • Peripheral Nerve Injuries
  • Pain Management

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not Applicable.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See:

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not Applicable.

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  • Deceased Gary Heit passed away in February 2023.

  • Contributors All authors either made a substantial contribution to the study concept, design, and/or analysis, or they enrolled at least one study subject. All authors approved the final version of the manuscript. SK is responsible for the overall content as the guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled decision to publish.

  • Funding This study was sponsored by Nalu Medical.

  • Competing interests GH is a consultant at Nalu Medical, Agitated Solutions, and a co-founder of Nesos. PS is a consultant for Nalu Medical, Saluda, SPR therapeutics and Medtronic. He is the Chief Medical Officer at electroCore. SK is an employee at Nalu Medical. JM is a consultant at Nalu Medical and owns stock in Nalu Medical. JH is a speaker and consultant for Nalu Medical. MJD consults for Avanos, Nalu, SPR Therapeutics; receives research support from Abbott, Avanos, Averitas, Mainstay, Nalu, Nature Cell, Saol, SPR Therapeutics and Vivex; and owns stock options in SPR Therapeutics, SynerFuse and Virdio.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.