Peripheral Nerve Stimulation for Neuropathic Pain

(M-SPA Trial)

Overseen By Jennifer Hah, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stanford University

Must be taking: Analgesics

Disqualifiers: Cancer, Diabetic neuropathy, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 months

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Peripheral Nerve Stimulation (PNS) for individuals with chronic neuropathic pain in the lower back, pelvis, or legs. It seeks to determine how well PNS works compared to regular pain treatments. Participants may receive either standard medical care or a combination of PNS and standard care. Suitable candidates have experienced persistent nerve pain for at least six months, linked to a nerve injury in the lower body, and have found some success with nerve blocks (temporary numbing injections). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment option.

Do I have to stop taking my current medications for the trial?

You will need to keep your pain medication dosage stable for at least 30 days before the trial and cannot try new pain medications for three months after joining. You must also avoid taking pain medications for 12 hours before certain tests.

What prior data suggests that this peripheral nerve stimulation therapy is safe for treating chronic neuropathic pain?

Research has shown that peripheral nerve stimulation (PNS) can effectively treat nerve pain. Many patients experience long-lasting pain relief with PNS devices. Studies indicate that about two-thirds of patients report at least a 50% reduction in pain, marking a significant improvement.

Regarding safety, some side effects have been reported, including infections, movement of device parts, and skin issues at the device site. However, these problems are uncommon.

Overall, PNS appears to be a well-tolerated option for managing long-term pain. Patients should consult their healthcare providers to address any concerns and fully understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuropathic pain?

Peripheral Nerve Stimulation (PNS) is unique because it offers a new way to manage neuropathic pain by directly targeting the nerves responsible for transmitting pain signals. Unlike standard treatments like medications that often come with side effects or require long-term use, PNS uses electrical impulses to modulate nerve activity, potentially reducing pain more effectively and with fewer side effects. Researchers are excited about this approach because it combines PNS with Conventional Medical Management (CMM), potentially enhancing pain relief while minimizing the reliance on medications alone.

What evidence suggests that peripheral nerve stimulation is effective for neuropathic pain?

Research has shown that peripheral nerve stimulation (PNS), a treatment under study in this trial, can alleviate long-lasting nerve pain. Many patients have reported enduring pain relief with PNS, experiencing a significant reduction in pain levels. In one study, the average pain score decreased from 8.5 to 4.25 over a year. Another study found that about two-thirds of patients experienced at least 50% pain relief. These results suggest that PNS might reduce pain for individuals with chronic nerve pain in the lower back, pelvis, and legs. Participants in this trial may receive PNS combined with Conventional Medical Management (CMM) or CMM alone. ^{1 3 4 5 6}

Who Is on the Research Team?

Jennifer Hah, MD, MS.

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for people with chronic pain in the lower back, leg, or due to ilioinguinal neuralgia. Participants should be experiencing neuropathic pain and can commit to a year-long study with monthly check-ins and several testing sessions. It's not specified who cannot join, but typically those with conditions that could interfere with the study or their safety would be excluded.

Inclusion Criteria

I am an adult with nerve pain in one leg due to a nerve injury or condition.

Patients enrolled in this study must already have been referred for or have an existing order for PNS implant prior to consent and enrollment in this study as part of routine medical care. Must have a positive response (at least 50% pain relief) to diagnostic nerve block(s) at the suspected site(s) of CNP. Must have chronic (at least 6 months duration), intractable peripheral neuropathic pain with any nociceptive pain less prominent than neuropathic pain. Must have stable dosage of analgesic medications for at least 30 days and be willing to refrain from trialing new analgesic medications for three months after randomization. Must have worst pain intensity of ≥5/10 on the Numeric Rating Scale (NRS) of Pain at the lower extremity CNP-PI site at enrollment and <5/10 on the NRS elsewhere over the entire body. Must be fluent in English writing, reading, and speaking. Must have the ability and willingness to complete online assessments. Must be willing to refrain from physical activity or exercise causing muscle and/or joint soreness for 48 hours prior to QST, pain medications for 12 hours prior to QST, and alcohol and nicotine on the day of QST

Exclusion Criteria

I have nerve damage due to diabetes.

I have an active cancer diagnosis, either metastatic or localized.

I have long-lasting nerve pain from a spinal cord or brain injury, or multiple sclerosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including PET/MRI and QST

1 week

1 visit (in-person)

Treatment

Participants receive either CMM or PNS+CMM with monthly remote assessments

12 months

Monthly remote assessments

Quantitative Sensory Testing (QST)

QST performed at baseline, 30 days, 3 months, and 6 months for PNS patients

6 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Peripheral Nerve Stimulation

Trial Overview The trial is testing if adding Peripheral Nerve Stimulation (PNS) to regular medical care helps more than just standard treatment alone for chronic neuropathic pain. Patients are randomly chosen to receive either just conventional care or combined PNS and conventional care, followed over a year.

How Is the Trial Designed?

Group I: Peripheral Nerve Stimulation + Conventional Medical Management (PNS+CMM) Experimental Treatment 2 Interventions

Group II: Conventional Medical Management (CMM) ONLY Active Control 1 Intervention

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Kansas Medical Center

Collaborator

Trials

527

Recruited

181,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Peripheral nerve stimulation (PNS) is an advanced treatment option for patients with peripheral neuropathic pain, particularly when other treatments have failed, highlighting its role as a specialized analgesic technique.

In a reported case of intractable neuropathic pain after multiple surgeries, PNS provided significant pain relief after previous treatments were ineffective, demonstrating its efficacy in managing chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral nerve stimulation in intractable neuropathic pain. Kozak, J., Kobesova, A., Vrba, I., et al.[2013]

A new training curriculum for Peripheral Nerve Stimulation (PNS) has been developed by a multidisciplinary task force to standardize education and improve proficiency in this effective treatment for chronic pain.

The curriculum includes defined milestones for learners at different levels (early, advanced, and practitioner) and covers essential skills such as professionalism, medical knowledge, and procedural skills, ensuring comprehensive training in PNS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society. Kalia, H., Abd-Elsayed, A., Malinowski, M., et al.[2023]

Ultrasound-guided placement of peripheral nerve stimulation electrodes in cadaver specimens showed no gross nerve damage and allowed for precise positioning near the targeted nerves, indicating a safe method for potential clinical use.

Out of the three electrodes placed, only one showed significant migration after 21 hours of simulated activity, suggesting that the anchoring technology used may effectively minimize electrode movement during normal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of ultrasound-guided percutaneous placement of peripheral nerve stimulation electrodes and anchoring during simulated movement: part two, upper extremity. Huntoon, MA., Hoelzer, BC., Burgher, AH., et al.[2019]

Peripheral nerve stimulation (PNS) is an effective technique for managing various types of chronic and acute pain by using electrical stimulation to inhibit pain signal transmission in both central and peripheral pathways.

PNS works by inhibiting specific pain fibers in the central nervous system and downregulating inflammatory mediators and neurotransmitters involved in pain signaling, making it a versatile option for treating conditions like post-surgical pain, headaches, and phantom limb pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of Action of Temporary Peripheral Nerve Stimulation. Abd-Elsayed, A., Attanti, S., Anderson, M., et al.[2023]

The distal to proximal neurostimulator lead revision technique is a safe and effective method for adjusting lead positions in patients with chronic pain, as demonstrated in a case series of 3 patients.

All patients experienced over 50% pain reduction at long-term follow-up, indicating that this technique can provide significant relief without the need for replacing the entire neurostimulator system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A technique of distal to proximal revision of peripheral neurostimulator leads: technical note. Mammis, A., Mogilner, AY.[2014]

A case study of a 53-year-old woman with chronic lower extremity neuropathic pain showed that a design-specific peripheral nerve stimulation (PNS) device provided significant pain relief and improved functionality for two years after implantation.

This case highlights the effectiveness of modern PNS technology, suggesting it may be a preferable option over spinal cord stimulation for patients with isolated extremity pain, particularly those with spinal abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancement in Neuromodulation Technology with the Innovation of Design-Specific Peripheral Nerve Stimulators: Sural Nerve Stimulation for Radiculopathy. Langford, B., Mauck, WD.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11801347/

Real-world long-term outcomes of peripheral nerve stimulation Patients report clinically meaningful long-term pain relief after receiving PNS through both 60-day and permanent implant systems.

2. link.springer.com link.springer.com/article/10.1007/s40122-024-00659-6

Peripheral Nerve Stimulation for Neuropathic Pain ... In the final follow-up, which included 12 participants, the median pain reduction was 47.50% with a mean of 52.30%, ranging from 0.00% to 100.00 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925001382

Safety and Efficacy of Magnetic Peripheral Nerve ... The primary efficacy end point was a ≥50% reduction in diabetic neuropathy pain intensity at day 30, with no increase in baseline pain ...

4. mdpi.com mdpi.com/2077-0383/14/11/3964

Patient-Reported Outcomes with Peripheral Nerve ... Results: PNS led to marked improvements in pain-related outcomes. The average pain intensity scores dropped from 8.5 at baseline to 4.25 at one year, and pain ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8586061/

Peripheral Nerve Stimulation for Chronic Pain: A Systematic ... The evidence suggests that approximately two-thirds of patients with peripheral neuropathic pain will have at least 50% sustained pain relief.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715925000315

An Analysis of the MAUDE Data base and Implications for ... Our analysis of the MAUDE data base revealed that infection, lead migration, and skin erosion were the most commonly reported AEs associated with the use of PNS ...