Quantitative Assessment of Painful Diabetic Peripheral Neuropathy After High Frequency Spinal Cord Stimulation

Study Overview
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Brief Summary
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Will participants with painful lower extremity diabetic peripheral neuropathy (DPN) that are treated with high frequency spinal cord stimulation (HF10 SCS) have improvements in lower extremity peripheral nerve function?

Detailed Description
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This research study is being conducted to find out if spinal cord stimulation (SCS) can improve nerve function. SCS is FDA approved for the treatment of intractable neuropathic (nerve) pain related to diabetic peripheral neuropathy. With SCS a wire is placed in the epidural space and the spinal cord is stimulated to interrupt the pain signal coming from the legs. The spinal cord stimulator is a device similar to a pacemaker (which helps treat abnormal rhythms of the heart). Recent studies have suggested that SCS with high frequencies can improve nerve function for subjects with painful peripheral neuropathy therefore, the investigators are looking to measure changes in nerve function after SCS for treatment of painful diabetic peripheral neuropathy. The purpose of this research is to gather information on the effect of high frequency spinal cord stimulation (HF10) on nerve function with a spinal cord stimulator.

Official Title
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Quantitative Assessment of Painful Diabetic Peripheral Neuropathy After High Frequency Spinal Cord Stimulation: (QUANT) HF10 Study

Conditions
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Painful Diabetic Neuropathy

Intervention / Treatment
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* Device: High Frequency Spinal Cord Stimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Refractory predominantly lower extremity neuropathic pain for > 1 year Presence of length dependent peripheral neuropathy on sudomotor testing Completed spinal cord stimulation trial with 40% or greater pain reduction from baseline Failed medication trials or contraindication to gabapentin medications (gabapentin, pregabalin) and/or serotonin/norepinephrine reuptake inhibitors (tricyclic antidepressant (TCA) or duloxetine or venlafaxine) Average pain score on a visual analog scale (VAS) of ≥ 5 (with 0 representing no pain and 10 the worst pain imaginable) Appropriate surgical candidate for spinal cord stimulator Exclusion Criteria: Severe Autonomic Neuropathy as measured by the composite autonomic scoring scale (10 point scale) with a score ≥ 7 History of sympathectomy Uncontrolled arterial hypertension (Systolic Blood Pressure >160) Baseline Foot TcPO2 < 10 mmHg to exclude patients with severe peripheral arterial disease Hemoglobin A1c > 8% Stable opioid regimen with oral morphine equivalent ≥ 100 mg/day Alternative principle cause for peripheral neuropathy or lower extremity neuropathic pain Disruptive psychiatric disorder (screened for during preoperative psychiatric evaluation) Pending litigations Women of child bearing potential unwilling to use contraception or found to be pregnant as part of perioperative screening Patients unable to hold medications that would impact autonomic testing

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spinal Cord Stimulator Implant<br>Spinal Cord Stimulator implant | Device: High Frequency Spinal Cord Stimulator<br>* The SCS implant will follow standard clinical practice for these FDA approved indications. Two percutaneous leads will be placed in the posterior spinal epidural space under radiographic guidance and attached to either an external stimulator (trial phase) or a subcutaneously implanted impulse generator (IPG). Intraoperative impedance testing will be performed to ensure electrical integrity. Patients with HF10 SCS will receive 30 µs pulses delivered at 10,000 Hz with amplitude adjusted to optimal analgesic response. Programming will occur postoperatively and as needed based on patient feedback in standard clinic visits. .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Assessment | Pain measurement using a Visual Analog Pain Scale by placing an X in the box to indicate the severity of pain from no pain to intolerable pain. The X in the box translates to a score of zero for no pain and increases by an additional 0.5 up to a high score of 10 which would be intolerable pain. | Baseline, 12 months | 
| Neuropathy Symptoms and Change (NSC) Score | Validated questionnaire that evaluates change in neuropathy symptoms, including symptoms of weakness, sensory symptoms, and autonomic symptoms. Answers to questionnaire are yes/no and if yes, then degree of severity is evaluated with a plus one(slight), plus two (moderate) and plus three (severe). Questionnaire screens the presence and severity of diabetic peripheral neuropathy. Change in severity of symptoms are compared over time. Total scores range from 0 - 114, lower scores reflect no neuropathy symptoms, higher scores reflect more neuropathy symptoms. | baseline, 12 months | 
| Oswestry Disability Index | Questionnaire examines perceived level of disability in 10 everyday activities of daily living including pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life and traveling. The 6 statements are scored from 0 to 5 scale, zero meaning no disability. The final score ranges from 0-100 with a score of 0-20 equals minimal disability, 21-40 equals moderate disability, 41-60 equals severe disability, 61-80 equals crippled and 81-100 equals bed-bound. | Baseline, 12 months | 
| Neuropathy Impairment Score (NIS) | Subject's scores neuropathic deficits using a scale of 0-4 (zero=normal, 4=paralysis) to measure muscle weakness. The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244. Lower scores indicate higher function, higher scores indicate lower function. | Baseline, 12 months | 
| Lower Limb Function Test | Test for lower limb function in which the subject will need to walk on toes, walk on heels, and arise from kneeled position, each test is marked as not applicable, normal or abnormal. The examination assesses each component for the left and right side separately. If the test is normal, it is given a score of 0, and if it is abnormal, a score of 1. Not applicable scores a zero. Total scores range 0-6. Therefore, the maximum score of 6 indicates abnormality in all 3 components bilaterally and a minimum score of 0 indicates a normal result for all 3 components bilaterally. | Baseline, 12 months | 
| Modified Leads Assessment of Neuropathic Symptoms and Signs | Questionnaire to identify and analyze pain by answering yes/no which translates to scores from 0-24. A score of 12 or more suggests pain of predominantly neuropathic origin. | baseline, 12 months | 
| Positive Pain | Numeric Rating Scale used to assess pain from a scale of 0 (no pain) to 10 (worst possible pain) | baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Health Questionnaire | Screens for the presence and severity of depression with 9 questions in a scale of 0-3. Zero=not at all, 1=several days, 2=more than half the days, 3=nearly every day. Total score range 0 - 27. A total score of 0-4=minimal depression, 5-9=mild depression, 10-14=moderate depression, 15-19=moderately severe depression, 20-27=severe depression | Baseline, 12 months | 
| Height | Subjects calculated height in centimeters. | Baseline, 12 months | 
| Weight | Subjects calculated weight in kilograms | Baseline, 12 months | 
| Body Mass Index (BMI) | Subject's BMI calculated as weight in kilograms divided by height in meters squared. Uses measurements of height and weight obtained during study (with appropriate metric conversions) | Baseline, 12 months | 
| Hemoglobin A1c | Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An A1C level below 5.7 percent is considered normal. Reported as percentage of glycated hemoglobin | Baseline, 12 months | 
| Forearm Sweat Volume Quantitative Axon Reflex Sweat Test (Q-SWEAT) | Test that measures the rate and volume of sweat to determine the severity and pattern of autonomic disorders. As measured by µL/cm² | baseline, 12 months | 
| Proximal Leg Laser Doppler Flowmetry (LDF) | Laser Doppler velocimetry is used in hemodynamics research as a technique to partially quantify blood flow in human tissues such as skin. Within the clinical environment, the technology is often referred to as laser Doppler flowmetry (LDF). As measured in perfusion units (p.u.) | Baseline, 12 months | 
| Extensor Digitorum Brevis Muscle Nerve Conduction | A nerve conduction study (NCS) is a medical diagnostic test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body. As measured by amplitude (AMP) milliamp (mA) | Baseline, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord stimulation, type 2 diabetes