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

134 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a mechanistic randomized controlled trial of 134 patients with lower extremity chronic neuropathic pain randomized to stable conventional medical management (CMM) or combined CMM and peripheral nerve stimulation therapy (PNS+CMM). All participants will undergo baseline and monthly remote assessments for up to 1 year. Quantitative sensory testing (QST) will be performed in all participants at baseline, 30 days, and 3 months, with an additional QST session in PNS implanted patients at 6 months. The local expression of sigma-1 receptors in chronic pain allows for visualization of peripheral pain generators, and the investigators will utilize a novel PET radiotracer highly selective for the sigma-1 receptor correlating with local receptor density and pain symptoms. 78 patients (39 in each arm, only at Stanford) will undergo \[18F\]FTC-146 PET/ MRI at baseline. 5 patients will also receive PET/CT of the lower extremities at baseline. These 78 patients will also receive \[18F\]FTC-146 PET/CT at 3 months. The investigators will characterize treatment interactions with participant attributes and baseline QST pain sensitivity measures in predicting treatment response; examine depression and physical function as mediators of treatment response; compare longitudinal pain, depressive symptom, pain catastrophizing, physical function, and QST trajectories across treatments, compare acute QST responses to PNS after stable implantation, and determine whether peripheral imaging markers correlate with baseline pain and treatment response.

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 data supports the effectiveness of the treatment Peripheral Nerve Stimulation for neuropathic pain?

Research shows that Peripheral Nerve Stimulation (PNS) can provide significant pain relief for people with chronic neuropathic pain, especially when other treatments have failed. In one case, a patient experienced substantial pain reduction after PNS, and another study reported long-term pain relief for two years with a design-specific PNS device. ^{1 2 3 4 5}

Is peripheral nerve stimulation (PNS) generally safe for humans?

Peripheral nerve stimulation (PNS) has been used since the 1960s and is considered safe, with recent advancements in technology improving its safety profile. However, there can be hardware-related complications that may require adjustments or revisions. ^{1 2 4 6 7}

How does peripheral nerve stimulation differ from other treatments for neuropathic pain?

Peripheral nerve stimulation (PNS) is unique because it uses electrical impulses to block pain signals in the nerves, offering relief where other treatments have failed. Unlike medications, PNS is a specialized, minimally invasive procedure that can provide long-term pain relief for chronic and difficult-to-treat neuropathic pain. ^{1 2 3 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

Peripheral nerve stimulation in intractable neuropathic pain. [2013]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain. [2019]

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

Considerations in permanent implantation of peripheral nerve stimulation (PNS) for chronic neuropathic pain: An international cross-sectional survey of implanters. [2022]

5. England 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. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society. [2023]

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

Mechanism of Action of Temporary Peripheral Nerve Stimulation. [2023]

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

Peripheral nerve stimulation for neuropathic pain. [2023]