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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03769675

Enrollment

Registered

2018-12-07

Start date

2018-11-20

Completion date

2022-04-15

Last updated

2023-04-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Painful Diabetic Neuropathy

Keywords

spinal cord stimulation, type 2 diabetes

Brief summary

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

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.

Interventions

DEVICEHigh Frequency Spinal Cord Stimulator

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. .

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Pain Assessment	Baseline, 12 months	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.
Neuropathy Symptoms and Change (NSC) Score	baseline, 12 months	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.
Oswestry Disability Index	Baseline, 12 months	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.
Neuropathy Impairment Score (NIS)	Baseline, 12 months	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.
Lower Limb Function Test	Baseline, 12 months	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.
Modified Leads Assessment of Neuropathic Symptoms and Signs	baseline, 12 months	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.
Positive Pain	baseline, 12 months	Numeric Rating Scale used to assess pain from a scale of 0 (no pain) to 10 (worst possible pain)

Secondary

Measure	Time frame	Description
Patient Health Questionnaire	Baseline, 12 months	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
Height	Baseline, 12 months	Subjects calculated height in centimeters.
Weight	Baseline, 12 months	Subjects calculated weight in kilograms
Body Mass Index (BMI)	Baseline, 12 months	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)
Hemoglobin A1c	Baseline, 12 months	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
Forearm Sweat Volume Quantitative Axon Reflex Sweat Test (Q-SWEAT)	baseline, 12 months	Test that measures the rate and volume of sweat to determine the severity and pattern of autonomic disorders. As measured by µL/cm²
Proximal Leg Laser Doppler Flowmetry (LDF)	Baseline, 12 months	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.)
Extensor Digitorum Brevis Muscle Nerve Conduction	Baseline, 12 months	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)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Spinal Cord Stimulator Implant (SCS) Spinal Cord Stimulator implant High Frequency Spinal Cord Stimulator: The SCS implant followed standard clinical practice for FDA approved indications: Two percutaneous leads were placed in the posterior spinal epidural space under radiographic guidance and attached to either an external stimulator or a subcutaneously implanted impulse generator (IPG). Intraoperative impedance testing was performed to ensure electrical integrity. Patients with HF10 SCS received 30 µs pulses delivered at 10,000 Hz with amplitude adjusted to optimal analgesic response. Programming occurred postoperatively and as needed based on patient feedback in standard clinic visits.	10
Total	10

Arm

Count

Spinal Cord Stimulator Implant (SCS)

Spinal Cord Stimulator implant High Frequency Spinal Cord Stimulator: The SCS implant followed standard clinical practice for FDA approved indications: Two percutaneous leads were placed in the posterior spinal epidural space under radiographic guidance and attached to either an external stimulator or a subcutaneously implanted impulse generator (IPG). Intraoperative impedance testing was performed to ensure electrical integrity. Patients with HF10 SCS received 30 µs pulses delivered at 10,000 Hz with amplitude adjusted to optimal analgesic response. Programming occurred postoperatively and as needed based on patient feedback in standard clinic visits.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	1

Baseline characteristics

Characteristic	Spinal Cord Stimulator Implant (SCS)	—
Age, Continuous	55.0 years	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment United States	10 participants	—
Sex/Gender, Customized Female	5 Participants	—
Sex/Gender, Customized F-Transgender	1 Participants	—
Sex/Gender, Customized Male	4 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 10
other Total, other adverse events	0 / 10
serious Total, serious adverse events	0 / 10

Outcome results

Primary

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.

Time frame: Baseline, 12 months