Mechanisms of Stimulation for Pain Alleviation (M-SPA)

This is a mechanistic randomized controlled trial of patients with chronic neuropathic pain (CNP) in the lower back, pelvis, and lower extremities, randomized to conventional medical management (CMM) or combined CMM and peripheral nerve stimulation therapy (PNS+CMM). Our goal is to compare treatment outcomes and trial response rate across the control and interventional device groups.

Study Overview

• Status: Recruiting
• Conditions: Chronic Neuropathic Pain; Chronic Neuropathic Pain in the Low Back and Legs; Peripheral Nerve Stimulation
• Intervention / Treatment: Procedure: Conventional Care Regimen; Device: Peripheral Nerve Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Principal Investigator: Jennifer Hah, MD, MS
      • Contact: Jennifer Hah; Phone Number: 6507243193; Email: jhah@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria for study participants

Adults aged 18 or older with clinically diagnosed unilateral CNP in the lower back, pelvis, or lower extremities, 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).14 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 therapy (either Nalu or SPR SPRINT), 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.

Fluent in English writing, reading, and speaking

Ability and willingness to complete online assessments

Williness to refrain from physical activity for at least 7 days post-lead placement.

Willingness to refrain from physical activity or exercise causing muscle and/or joint soreness for 48 hours prior to QST, illicit drugs (marijuana) for 12 hours, as-needed (PRN) pain medications (e.g., NSAIDs, acetaminophen, opioids) for 12 hours prior to QST, and alcohol and nicotine on the day of QST prior to testing*

Exclusion Criteria:

Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)

Active 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 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

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*

*QST Inclusion/Exclusion Criteria. Participants can still be enrolled iif they have the QST-only exclusionary criteria have the QST-only exclusionary criteria, but QST will be modified based on responses

Additional Exclusion Criteria for Subjects receiving PET/MRI and PET/CT imaging at Stanford:

Prior radiation exposure of >2 rem total within the last 12 months

Standard contraindications that would preclude MRI including pacemakers or other electronic implants, metal foreign objects or fragments in the eye or body, and aneurysm clips.

Claustrophobia

Inability to understand and communicate with the investigators to complete the study related questionnaires

Females with positive pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Medical Management (CMM) ONLY	Procedure: Conventional Care Regimen; CMM-Only participants will receive conventional medical management for the duration of their time in the study.
Experimental: Peripheral Nerve Stimulation + Conventional Medical Management (PNS+CMM)	Procedure: Conventional Care Regimen; CMM-Only participants will receive conventional medical management for the duration of their time in the study.; Device: Peripheral Nerve Stimulation; This trial studies 2 FDA approved peripheral nerve stimulation devices that may reduce pain by sending electrical pulses to the nerve. The SPR SPRINT PNS System, a matchbox-sized, battery-powered wearable stimulator that uses a Mircrolead to deliver stimulation for pain relief. There is a small wireless hand-held remote that is used to activate/ adjust intensity of stimulation. Stimulation delivered by this device may interrupt pain signals and increase non-pain signals. The SPR SPRINT device is used for 60 days before the percutaneous Microlead(s) are removed. The Nalu PNS System, a dime-sized micro-implantable pulse generator (IPG) leveraging advanced microelectronics. The micro-IPG is powered by an externally worn therapy disc via radiofrequency worn over the IPG site with an adhesive clip applied to the skin or a relief belt. The device is remote-controlled by patients via an app.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Response: defined as 50% relief of average pain intensity at the area of lower back, pelvic, or lower extremity CNP. We will compare the means of a three-day diary of numeric rating scale of pain (NRS) intensity scores (0-10 scale)	We will 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.	Baseline to Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial Response Rate	Defined as 50% relief of average pain intensity comparing 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. This outcome will be assessed either 15 days after baseline assessments among participants randomized to CMM, 15 days after Nalu PNS trial lead placement, or 15 days after SPR Sprint PNS microlead placement.	Baseline to 15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Remission Rate	Average pain intensity les s than 2.5 out of 10 (at the CNP site) at 3 months measured over three days	From baseline to 3 months
Minimum Treatment Response Rate	30% relief comparing average pain intensity at baseline at the area of lower extremity CNP to scores at 3 months. Scores will be averaged over 3 days pre- and post-surgery.	From baseline to 3-month followup
Change in Neuropathic Pain Symptoms	Measured by the Neuropathic Pain Symptom Inventory (NPSI) with a total score ranging from 0 to 100, with higher scores indicating greater neuropathic pain intensity. Measured monthly to 3 months.	MONTHLY from baseline to 3-month followup
Change in Pain Distribution	Total number of affected sites measured at 3 months on the Michigan Body Map	From baseline to 3-month followup
Change in Pain Interference	Mean score of pain interference items rated on a 0-10 scale at 3 months.	From baseline to 3-month followup
Change in Physical Functioning	Measured by PROMIS Physical Functioning Short Form 6b at 3 months, rating difficulty in basic physical activities on a 1-5 scale from most to least difficult	From baseline to 3-month followup
Change in Sleep	Measured by PROMIS Sleep Disturbance 6a at 3 months, rating sleep quality measures on a 1-5 scale from very good to very poor	From baseline to 3-month followup
Change in Pain Catastrophizing	Measured by the Pain Catastrophizing Scale-Short Form 6 (PCS) score at 3 months, rating participant's emotional responses to pain from "not at all" to "all the time"	From baseline to 3-month followup
Minimum Patient Improvement Rate	Measured by the Patient Global Impression of Change (PGIC), rating change to overall patient pain status with 7 responses from 1-very much improved to 7-very much worse. Defined as a response of 1,2, or 3 at 3 months	From baseline to 3-month followup
Longitudinal Change in Mood - Depression	Measured MONTHLY by PROMIS Depression 4A, rating depressive symptoms on a 5-level scale from "never" to "always"	Through study completion, up to 1 year
Longitudinal Change in Mood - Anxiety	Measured MONTHLY by PROMIS Anxiety 4A, rating anxious symptoms on a 5-level scale from "never" to "always"	Through study completion, up to 1 year
Longitudinal Change in Mood - PHQ9	Measured MONTHLY by Patient Health Questionnaire (PHQ-9), rating depressive and anxious habits on a 4-level scale from "not at all" to "nearly every day"	Through study completion, up to 1 year
Change in health-related quality of life (QoL)	Measured by the PROMIS-Preference (PROPr) score serving as a measure of health-related QOL calculated from previous measures: PROMIS Cognitive Function, depression, fatigue, pain interference, physical function, Ability to Participate in Social Roles and Activities, and sleep disturbance assessed at 3 months; ranked on a 0-1 scale where 0 is the utility of being dead and 1 is the utility of full health.	From baseline to 3-month followup
Change in Opioid Dose	Change in daily OME use from baseline to use at 3 months. Comparing the average use over three days at baseline to average use over three days at 3 months to account for as-needed dosing. In addition, we will compare average daily OME as determined by State PDMP prescription at baseline and at 3 months.	From baseline to 3-month followup

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); University of Kansas Medical Center
• Investigators: Principal Investigator: Jennifer Hah, MD, MS., Stanford University

Publications and helpful links

Helpful Links

• SPR Therapeutics - SPRINT PNS System Overview
• NALU Neurostimulation - NALU PNS System Overview

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: SPRINT PNS; NALU PNS
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 76560; RM1NS128956-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes