Comparison of 10 kHz SCS Combined With CMM to CMM Alone in the Treatment of Neuropathic Limb Pain

Study Overview
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Brief Summary
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This post-market study is being conducted to document comparative safety, clinical effectiveness, and cost-effectiveness of the addition of HF10™ therapy to CMM compared with CMM alone in subjects with chronic, intractable, neuropathic lower limb pain due to diabetic neuropathy (Painful Diabetic Neuropathy or PDN). This study is a multi-center, prospective, randomized comparison of the two treatments.

Official Title
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A Post-Market, Multicenter, Prospective, Randomized Clinical Trial Comparing 10 kHz Spinal Cord Stimulation (HF10™ Therapy) Combined With Conventional Medical Management to Conventional Medical Management Alone in the Treatment of Chronic, Intractable, Neuropathic Limb Pain

Conditions
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Painful Diabetic Neuropathy

Intervention / Treatment
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* Device: Senza HF10 Therapy
* Other: CMM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been clinically diagnosed with painful diabetic neuropathy (PDN) of the lower limbs. Average pain intensity of ≥ 5 out of 10 cm on the VAS in the lower extremities at enrollment. Have stable neurological status. Be on a stable analgesic regimen. Be 22 years of age or older at the time of enrollment. Be an appropriate candidate for the surgical procedures required in this study. Be capable of subjective evaluation, able to read and understand English-written questionnaires, and able to read, understand and sign the written informed consent in English. Be willing and capable of giving informed consent. Be willing and able to comply with study-related requirements, procedures, and scheduled visits. Exclusion Criteria: Have a diagnosis of a lower limb mononeuropathy, have had a lower limb amputation, or have large (≥3 cm) and/or gangrenous ulcers of the lower limbs. Have a BMI ≥ 40. Currently prescribed a daily opioid dosage > 120 mg morphine equivalents. Have a medical condition or pain in other area(s), not intended to be treated in this study. Have a current diagnosis of a progressive neurological disease such a multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, brain or spinal cord tumor, central deafferentation syndrome, Complex Regional Pain Syndrome, acute herniating disc, severe spinal stenosis and brachial plexus injury. Have a current diagnosis or condition such as a coagulation disorder, bleeding diathesis, platelet dysfunction, low platelet count, severely diminished functional capacity due to underlying cardiac/pulmonary disease, symptomatic uncontrolled hypertension, progressive peripheral vascular disease or uncontrolled diabetes mellitus that presents excess risk for performing the procedure. Have failed prior SCS, dorsal root ganglion (DRG) stimulation, or peripheral nerve stimulation (PNS) trials for chronic intractable pain. Have significant spinal stenosis, objective evidence of epidural scarring and/or any signs or symptoms of myelopathy. Any previous history of surgery on the posterior elements (laminectomy, posterior fusion) resulting in a compromised epidural space. Be benefitting from an interventional procedure and/or surgery to treat lower limb pain. Have an existing drug pump and/or another active implantable device such as a pacemaker. Have a condition currently requiring or likely to require the use of diathermy or MRI that is inconsistent with Senza system guidelines in the Physician's Manual. Have either a metastatic malignant neoplasm or untreated local malignant neoplasm. Have a life expectancy of less than one year. Have a local infection at the anticipated surgical entry site or an active systemic infection. Be pregnant or plan to become pregnant during the study. Women of childbearing potential who are sexually active must use a reliable form of birth control, be surgically sterile, or be at least 2 years post-menopausal. Have within 6 months of enrollment a significant untreated addiction to dependency producing medications, alcohol or illicit drugs. Be concomitantly participating in another clinical study. Be involved in an injury claim under current litigation. Be a recipient of Social Security Disability Insurance (SSDI). Have a pending or approved worker's compensation claim. Have evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of pain, compliance with intervention and/or ability to evaluate treatment outcome.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HF10 therapy plus CMM<br>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management | Device: Senza HF10 Therapy<br>* Senza 10kHz Spinal Cord Stimulation<br>|
| Other: CMM Alone<br>Conventional Medical Management | Other: CMM<br>* Conventional Medical Management<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Safety and Effectiveness | Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores of 3 or Less | Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm. | 3 months | 
| Crossover Rates | Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up. | 6 months | 
| Responder Rates | Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS). | 6 months | 
| Remitter Rates | Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months). | 6 months | 
| Neurological Assessment | Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex). | 3 months | 
| Neurological Assessment | Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex). | 6 months | 
| Health-related Quality of Life | Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L). | 6 months | 
| Hemoglobin A1c | Difference between the treatment groups in the average percentage change from baseline in HbA1c levels. | 6 months |