Mechanisms of Stimulation for Pain Alleviation

Phase 3

Not yet recruiting

• Conditions: Chronic Neuropathic Pain in the Low Back and Legs; Peripheral Nerve Stimulation; Chronic Neuropathic Pain

• Registration Number: NCT06741579
• Lead Sponsor: Stanford University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-25
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-17
• Last Update Submitted: 2024-12-17
• Study First Posted: 2024-12-19
• Last Update Posted: 2024-12-19
• Study Start: 2025-01-01
• Primary Completion: 2028-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

• Adults aged 18 or older with clinically diagnosed unilateral lower extremity CNP defined (per IASP classification) as persistent or recurrent neuropathic pain caused by a peripheral nerve lesion, history of a plausible nerve trauma, pain onset in temporal relation to the trauma, and pain distribution within the innervation territory of a peripheral nerve (or nerves). Negative and positive sensory symptoms or signs must be compatible with the innervation territory of the affected nerve. Can be post-traumatic, post-surgical, nerve compression, nerve ischemia, peripheral nerve injury, painful scar, nerve entrapment, mononeuropathy, with or without loss of motor function
• 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 their routine medical care. Patients cannot receive a referral for PNS device as part of the study procedures.
• Positive response (at least 50% pain relief) to diagnostic nerve block(s) at the suspected site(s) of CNP
• Chronic (at least 6 months duration), intractable peripheral neuropathic pain; any nociceptive pain must be less prominent than the neuropathic pian.
• Stable dosage of analgesic medications for at least 30 days, and willingness to refrain from trialing new analgesic medications for three months after randomization
• Worst pain intensity of ≥5/10 on the Numeric Rating Scale (NRS) of Pain (0-10) at the lower extremity CNP-PI site at enrollment •Worst pain intensity of <5/10 on the NRS elsewhere over the entire body
• Fluent in English writing, reading, and speaking
• Ability and willingness to complete online assessments
• Willingness to refrain from physical activity or exercise causing muscle and/or joint soreness for 48 hours prior to QST, pain medications (e.g., NSAIDs, acetaminophen, opioids) for 12 hours prior to QST, and alcohol and nicotine on the day of QST*

Exclusion Criteria

• Unable to tolerate wearing external Therapy Disk with relief belt/adhesive clip in the planned location of the IPG
• Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)
• Cancer diagnosis, active malignant neoplasm (metastatic or local) or evidence of paraneoplastic syndrome
• Painful polyneuropathy (e.g., metabolic, autoimmune, familial, infectious disease, environmental toxins, treatment with neurotoxic drug)
• Chronic central neuropathic pain (e.g., spinal cord injury, brain injury, multiple sclerosis)
• Peripheral vascular disease
• Diabetic neuropathy
• Another pain diagnosis affecting the lower extremity CNP site that could interfere with study procedures, accurate reporting and/or could confound evaluation of study endpoints (e.g., post-herpetic neuralgia)
• Other active implantable devices (e.g., implantable cardioverter defibrillator, spinal cord stimulator, dorsal root ganglion stimulator, sacral nerve stimulator, deep brain stimulator, intrathecal pump)
• Pregnancy, breastfeeding, or planning to conceive
• Systemic infection or local infection at the anticipated PNS implant site
• Immunocompromised state
• Coagulation disorder, bleeding diathesis, platelet dysfunction, active anticoagulation
• Interventional procedure and/or surgery to treat CNP in the last 30 days (subjects should be enrolled 30 days after last procedure, for prior ablative treatment must be enrolled at least 3 months after last procedure)
• Untreated substance use disorder
• Participating in another clinical trial with an active treatment arm
• Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail)*
• Numbness or loss of sensation at the bilateral thumbnails, peripheral neuropathy in the hands, circulatory or sensory problem in the hands*
• Participants with a history of Raynaud's Syndrome*
• Participants with SBP ≥150 and/or DBP ≥100*

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Treatment Response: 50% relief of average pain intensity at lower extremity chronic neuropathic pain	From baseline to 3-month followup	Compare the mean of a three-day diary of numeric rating scale of pain (NRS) intensity scores (0-10 scale) at baseline to the mean of a three-day diary of NRS scores at 3 months comparing all participants randomized to CMM vs. PNS+CMM

Secondary Outcome Measures

Name	Time	Method
Trial Response: 50% relief of average pain intensity	From baseline to 15 days post-trial start	Compare the mean of a three-day diary of NRS scores at baseline to the mean of a three-day diary of NRS scores at 15 days comparing participants randomized to CMM vs. PNS+CMM

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Palo Alto, California, United States