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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device called the NSS-2 BRIDGE, worn on the ear to reduce post-surgery pain. The researchers aim to determine if this device can decrease the need for opioid painkillers by managing pain and possibly improving mood. Participants will receive either the active device or a non-active version (placebo) to compare results. This trial suits individuals scheduled for specific open abdominal or pelvic surgeries, such as colorectal cancer surgery or liver transplant, with an expected hospital stay of about 5 days. As an unphased trial, it allows participants to contribute to innovative pain management research without the constraints of traditional trial phases.

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 prior data suggests that the NSS-2 BRIDGE device is safe for reducing postoperative pain?

Research shows that the NSS-2 BRIDGE device is generally well-tolerated. Studies have demonstrated its significant effectiveness in relieving pain, particularly for those with abdominal pain syndrome. For instance, one study found that all participants experienced fewer withdrawal symptoms when using the device, highlighting its pain-reducing capabilities.

Another study on ear nerve stimulation confirmed that this method can help manage surgical pain. Although detailed safety information remains limited, these findings suggest the device is a potentially safe tool for pain management. Overall, current research indicates that the NSS-2 BRIDGE device is a promising and safe option for reducing pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for postoperative pain rely heavily on opioids, which can lead to unwanted side effects and dependency. The NSS-2 BRIDGE device is unique because it uses nerve stimulation to reduce pain, offering a non-drug alternative. It works by targeting branches of cranial nerves and the superficial cervical plexus through a percutaneous nerve field stimulator system. Researchers are excited because this approach could provide effective pain relief without the risks associated with opioids, potentially transforming how postoperative pain is managed.

What evidence suggests that the NSS-2 BRIDGE device is effective for reducing postoperative pain?

Research has shown that the NSS-2 BRIDGE device, which participants in this trial may receive, can significantly reduce the need for opioids after surgery. In earlier studies, patients using this device reported up to a 67% drop in opioid use after major abdominal surgery. Another study found a 60.2% decrease in opioid use, with patients still experiencing effective pain relief. These results suggest that the device might help manage pain without heavy reliance on opioids. The device works by stimulating nerves in the ear, which appears to help control pain signals. This offers a potential non-drug option for easing pain after surgery. Participants in this trial may also receive a sham device to compare the effectiveness of the NSS-2 BRIDGE device. ^{5 6 7 8 9}

Who Is on the Research Team?

Jacques E Chelly, MD, PhD, MBA

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9581440/

NSS-Bridge Device for Post-Cesarean Delivery Analgesia Our early research has suggested that the NSS2-Bridge successfully reduces postoperative pain and opioid requirements by up to 67% after major abdominal surgery ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03834142

NSS-2-BRIDGE Study for Total Knee and Hip ... The use of the NSS-2 BRIDGE device has been demonstrated to provide significant analgesia in patients with abdominal pain syndrome, and clinical trials are ...

3. medrxiv.org medrxiv.org/content/10.1101/2022.02.02.22270328v1.full-text

Reduction in postoperative opioid requirement associated ... Results Use of the NBD® resulted in a 26% overall reduction in OME with no difference in pain level expressed as the area under the curve ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1550728921003920

Auricular nerve stimulation using the NSS-2 BRIDGE ... Auricular nerve field electrical stimulation using NSS-2 BRIDGE® device (NBD®) was associated with 60.2% reduction in opioid consumption (mg of morphine PO ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34481724/

Auricular nerve stimulation using the NSS-2 BRIDGE ... This report suggests that NBD may represent an interesting alternative to control perioperative pain and limit opioid use following bariatric surgery.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03555266

NSS-2 BRIDGE Device in Post-Operative Pain Management The use of the NSS-2 BRIDGE device has been demonstrated to provide significant analgesia in patients with abdominal pain syndrome.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12247084/

Percutaneous auricular neuromodulation to treat pain after ... This pilot study demonstrates that percutaneous auricular neuromodulation is a feasible approach for managing pain in ambulatory surgical procedures.

8. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/DEN170018.pdf

De Novo Summary (DEN170018) Page 1 of 1 NSS-2 BRIDGE ... Overall, 73/73 (100%) subjects had a reduction in. COWS scores by 30 minutes with a minimum decrease of at least 31%. The results are shown in. Figure 6. Figure ...

9. rapm.bmj.com rapm.bmj.com/content/early/2022/07/15/rapm-2022-103777

Percutaneous auricular nerve stimulation ... These cases demonstrate that ambulatory percutaneous auricular neuromodulation is feasible and may be an effective analgesic and decreasing or even negating ...