Nerve Stimulation for Postoperative Pain

Recruiting at 3 trial locations

Overseen By Carly Riedmann, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jacques E. Chelly

Must not be taking: Opioids, Illicit drugs, Dexmedetomidine

Disqualifiers: Anxiety, Depression, Chronic pain, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 5 days

286 Participants Needed

Trial Summary

What is the purpose of this trial?

The NSS-2 BRIDGE® device (NSS stands for Neuro-Stimulation System) is a disposable device that stimulates the branches of cranial nerves and of the superficial cervical plexus innervating the ear. Because the stimulation of the nerves of the ear by the NSS-2 BRIDGE® device (NBD®) has been shown to modulate pain pathways in rodents, decrease abdominal pain in adolescents with inflammatory bile syndrome and due to the results of our preliminary pilot study, the investigators hypothesized that this technique may also be effective in reducing the requirement for postoperative opioids and provide a non-pharmacological alternative to perioperative opioid use. To establish the role that the stimulation of the nerves of the ear may have in reducing postoperative opioid requirement, the investigators are proposing to conduct a randomized, placebo controlled study in patients undergoing open abdominal or pelvic surgery requiring at least 5 days of hospitalization. Subjects who have signed an informed consent will be randomized in 2 groups (active NBD® group or inactive NBD® group). Furthermore, since preoperative and postoperative mood disorders have been shown to increase postoperative pain levels and opioid requirement by up to 50%, the investigators further hypothesize that the stimulation of the ear nerves by the NSS-2 BRIDGE® effects may be in part mediated by a reduction of the level of anxiety, depression and catastrophizing as assessed using validated questionnaires.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a chronic pain condition requiring daily opioid use, you may not be eligible to participate.

What data supports the effectiveness of the treatment NSS-2 BRIDGE for postoperative pain?

Research shows that the NSS-2 BRIDGE device can help reduce pain and the need for opioids after surgeries like gastric bypass and kidney donation by stimulating certain nerves in the ear. This nerve stimulation affects brain areas involved in pain control, suggesting it could be a useful non-drug option for managing postoperative pain. ^{1 2 3 4 5}

Is nerve stimulation for postoperative pain generally safe for humans?

Nerve stimulation, like spinal cord stimulation, is generally considered safe for humans, but it can have minor complications such as lead migration (when the wires move from their original position), pain at the implant site, and infections. These issues often require further medical attention but do not usually pose a serious threat to life or function. ^{6 7 8 9 10}

How does the NSS-2 BRIDGE treatment differ from other treatments for postoperative pain?

The NSS-2 BRIDGE treatment is unique because it uses auricular nerve stimulation (stimulation of nerves in the ear) to manage pain by affecting the brainstem and limbic system, which is different from traditional pain treatments that often rely on medications like opioids. ^{1 2 3 4 11}

Research Team

Jacques E Chelly, MD, PhD, MBA

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults over 18 who are scheduled for elective open abdominal or pelvic surgery with a planned hospital stay of about 5 days. It's not suitable for those unable to consent, with mood disorders, chronic pain or opioid use, allergies to opioids, laparoscopic surgery patients, pregnant women, ICU post-surgery patients on sedation, those with rapid recovery surgeries, substance abuse history or contraindications like pacemakers.

Inclusion Criteria

I am scheduled for colorectal cancer surgery at a specified UPMC hospital, following ERAS protocol.

I am over 18 years old.

Expected hospital stay of approximately 5 days

Exclusion Criteria

I have had surgery that was not planned in advance.

I was in the ICU after surgery, on a breathing machine, or given fentanyl for sedation.

I have been diagnosed with anxiety or depression, including thoughts of suicide.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the NSS-2 BRIDGE device or placebo immediately after surgery and wear it for 5 days

5 days

In-hospital stay for at least 5 days

Follow-up

Participants are monitored for changes in pain, opioid consumption, and emotional distress post-operatively

3 months

Regular assessments at 1 month and 3 months post-operative

Treatment Details

Interventions

• NSS-2 BRIDGE
• Sham NSS-2 BRIDGE

Trial Overview The study tests the NSS-2 BRIDGE device that stimulates ear nerves and may reduce the need for opioids after surgery. Participants will be randomly assigned to either an active device group or a placebo (inactive) group. The trial also examines if nerve stimulation can lower anxiety and depression which might affect pain levels and opioid needs.

Participant Groups

Group I: NSS-2 BRIDGE device Active Control 1 Intervention

This experimental arm involves the use of the NSS-2 BRIDGE device, which is a disposable device that stimulates the branches of cranial nerves and of the superficial cervical plexus innervating the ear. It will be placed on the subject immediately after surgery and worn for 5 days. It is a percutaneous nerve field stimulator (PNFS) system, that can be used as an aid to reduce the symptoms of opioid withdrawal, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination.

Group II: Placebo Bridge Placebo Group 1 Intervention

The sham group involves the use of 3 non-active points, or "nonfunctional points." The sham device will be placed on the subject immediately post-operatively and worn for 5 days just like the active group.

NSS-2 BRIDGE is already approved in United States for the following indications:

Approved in United States as NSS-2 BRIDGE for:

• Reduction of symptoms associated with opioid withdrawal

Who Is Running the Clinical Trial?

Jacques E. Chelly

Lead Sponsor

Trials

10

Recruited

710+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Masimo Corporation

Industry Sponsor

Trials

117

Recruited

13,500+

Katie Szyman

Masimo Corporation

Chief Executive Officer

BA from the University of St. Thomas, MBA from Harvard Business School

Dr. Bilal Muhsin

Masimo Corporation

Chief Medical Officer since 2024

MD from Harvard Medical School

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

The NSS2-Bridge device, used for percutaneous auricular nerve stimulation, was well-tolerated by patients after cesarean delivery, with an average tolerability score of over 75 mm on a visual analog scale, indicating high acceptability.

Patients using the active device had a higher rate of opioid-free hospitalizations (40%) compared to those with a placebo (20%) or no device (30%), suggesting potential for reducing opioid use post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial. Lim, G., Nowakowski, E., LaSorda, KR., et al.[2023]

The NSS-2 BRIDGE® device significantly reduced opioid requirements by 75.4% (from 33.6 mg to 8.3 mg) in kidney donor surgery patients, indicating its potential effectiveness in managing pain while minimizing opioid use.

Patients using the NSS-2 BRIDGE® device also experienced a notable 41.5% reduction in pain levels at 24 hours post-surgery, suggesting it may be a valuable tool for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular field nerve stimulation using the NSS-2 BRIDGE® device as an alternative to opioids following kidney donor surgery. Chelly, JE., Monroe, AL., Planinsic, RM., et al.[2022]

The NSS-2 BRIDGE device significantly reduced opioid consumption by 60.2% and pain levels by 28% in patients after gastric bypass surgery, indicating its potential effectiveness in pain management.

The device was well-tolerated by patients, with tolerability ratings considered excellent, suggesting it could be a viable alternative to traditional pain relief methods post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass. Ahmed, BH., Courcoulas, AP., Monroe, AL., et al.[2022]

In a case series involving 12 chronic pain patients with cancer, temporary peripheral nerve stimulation (PNS) was successfully used in 7 cases to alleviate oncologic pain, demonstrating its potential as a treatment option for patients who have not responded to other therapies.

The study highlighted the effectiveness of PNS in targeting specific neural pathways, including proximal spinal nerves and peripheral nerves, to manage various pain syndromes, although some cases did not achieve adequate pain relief, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study in Temporary Peripheral Nerve Stimulation in Oncologic Pain. Mainkar, O., Solla, CA., Chen, G., et al.[2022]

Peripheral nerve stimulation is emerging as a low-risk, opioid-sparing option for managing acute postoperative pain, which is important given the ongoing opioid crisis.

Current literature suggests that peripheral nerve stimulation can effectively enhance postsurgical analgesia, but further studies are needed to fully understand its short- and long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Role of Peripheral Nerve Stimulation in Postoperative Analgesia. Cho, AM., Xiong, JS., Burns, SL.[2023]

In a study of 115 procedures involving dorsal root ganglion (DRG) and spinal cord stimulation (SCS), the use of intraoperative neuromonitoring (IONM) resulted in a very low rate of complications, with only 1.7% experiencing minor adverse events that were easily corrected.

The findings suggest that IONM enhances the safety of neurostimulator device placement by allowing for immediate detection and correction of nerve irritation, potentially reducing the risk of long-term neurological complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Observational Study of Intraoperative Neuromonitoring as a Safety Mechanism in Placement of Percutaneous Dorsal Root Ganglion Stimulation and Spinal Cord Stimulation Systems. Hagedorn, JM., Deer, TR., Falowski, SM., et al.[2022]

In a study of 68 patients who had spinal cord stimulation paddle electrodes removed, the most common reason for removal was loss of coverage or effect (75%), indicating that while SCS is effective, it may not always provide lasting relief.

Postoperative complications occurred in 11.75% of patients, with two major complications requiring reoperation, highlighting that while SCS removal is generally safe, it does carry some risks that patients should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. Maldonado-Naranjo, AL., Frizon, LA., Sabharwal, NC., et al.[2022]

Spinal cord stimulation (SCS) can effectively reduce pain and improve quality of life for patients experiencing persistent postoperative neuropathic pain (PPNP) after lumbar spinal surgery, based on a review of 11 studies involving 542 patients.

While SCS is beneficial, it is associated with a notable rate of minor complications, such as lead migration (12%) and pain at the implant site (9%), particularly with surgically implanted devices, which may require additional surgical interventions but do not pose a direct threat to patient life or function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications related to the use of spinal cord stimulation for managing persistent postoperative neuropathic pain after lumbar spinal surgery. Shamji, MF., Westwick, HJ., Heary, RF.[2015]

A review of 707 patients receiving spinal cord stimulation (SCS) therapy showed that it is primarily used for complex regional pain syndrome (CRPS) and failed back surgery syndrome, which together accounted for 82% of cases, indicating its effectiveness in managing these specific pain conditions.

The study reported a low complication rate, with only 0.7% experiencing lead migration and no permanent neurological deficits or deaths, although hardware-related issues were more common, highlighting the importance of careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective review of 707 cases of spinal cord stimulation: indications and complications. Mekhail, NA., Mathews, M., Nageeb, F., et al.[2019]

In a study of 158 patients with failed back surgery syndrome (FBSS), spinal cord stimulation (SCS) showed only modest improvements in leg pain and function at 6 months, but these benefits diminished by 12 months, and less than 10% of patients achieved significant success overall.

Patients receiving SCS had higher rates of daily opioid use and experienced adverse events, with 19% of those who received a permanent stimulator having it removed within 18 months, indicating potential risks associated with this treatment compared to other pain management options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for failed back surgery syndrome: outcomes in a workers' compensation setting. Turner, JA., Hollingworth, W., Comstock, BA., et al.[2022]

Transcutaneous electrical nerve stimulation (TNS) was evaluated for pain relief during delivery in 147 women, with 44% reporting good to very good pain relief and another 44% experiencing moderate effects, indicating its efficacy as a pain management option.

The modified TNS technique showed no complications for either the mother or child, suggesting it is a safe primary pain relief method that can be used alongside conventional approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain relief during delivery by transcutaneous electrical nerve stimulation. Augustinsson, LE., Bohlin, P., Bundsen, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Auricular field nerve stimulation using the NSS-2 BRIDGE® device as an alternative to opioids following kidney donor surgery. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Pilot Study in Temporary Peripheral Nerve Stimulation in Oncologic Pain. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Emerging Role of Peripheral Nerve Stimulation in Postoperative Analgesia. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

An Observational Study of Intraoperative Neuromonitoring as a Safety Mechanism in Placement of Percutaneous Dorsal Root Ganglion Stimulation and Spinal Cord Stimulation Systems. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Complications related to the use of spinal cord stimulation for managing persistent postoperative neuropathic pain after lumbar spinal surgery. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Retrospective review of 707 cases of spinal cord stimulation: indications and complications. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for failed back surgery syndrome: outcomes in a workers' compensation setting. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Pain relief during delivery by transcutaneous electrical nerve stimulation. [2021]