Clinical trial NCT06741579: Mechanisms of Stimulation for Pain Alleviation
Official title: Mechanisms of Stimulation for Pain Alleviation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Chronic Neuropathic Pain in the Low Back and Legs
Peripheral Nerve Stimulation
Chronic Neuropathic Pain
Keywords: Nalu PNS Therapy
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Kansas Medical Center
First posted: 2024-12-19
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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 \&lt;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\*

Primary outcomes:
measure: Treatment Response: 50% relief of average pain intensity at lower extremity chronic neuropathic pain
timeFrame: From baseline to 3-month followup
Secondary outcomes:
measure: Trial Response: 50% relief of average pain intensity
timeFrame: From baseline to 15 days post-trial start
Other outcomes:
measure: Pain Remission Rate
timeFrame: From baseline to 3 months
measure: Minimum Treatment Response Rate
timeFrame: From baseline to 3-month followup
measure: Change in Neuropathic Pain Symptoms
timeFrame: MONTHLY from baseline to 3-month followup
measure: Change in Pain Distribution
timeFrame: From baseline to 3-month followup
measure: Change in Pain Interference
timeFrame: From baseline to 3-month followup
measure: Change in Physical Functioning
timeFrame: From baseline to 3-month followup
measure: Change in Sleep
timeFrame: From baseline to 3-month followup
measure: Change in Pain Catastrophizing
timeFrame: From baseline to 3-month followup
measure: Minimum Patient Improvement Rate
timeFrame: From baseline to 3-month followup
measure: Longitudinal Change in Mood - Depression
timeFrame: Through study completion, up to 1 year
measure: Longitudinal Change in Mood - Anxiety
timeFrame: Through study completion, up to 1 year
measure: Longitudinal Change in Mood - PHQ9
timeFrame: Through study completion, up to 1 year
measure: Change in health-related quality of life (QoL)
timeFrame: From baseline to 3-month followup
measure: Change in Opioid Dose
timeFrame: From baseline to 3-month followup
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
References: