Lidocaine for Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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Diabetic nerve pain [painful diabetic peripheral neuropathy] is a common medical problem with few reliably effective treatments. There is some evidence that sensory testing may help determine how individuals will respond to analgesic therapy. In this study, the investigators are evaluating the relationship between sensory testing and subject response to lidocaine infusion therapy.

Detailed Description
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Diabetic peripheral neuropathy [DPN] is caused by diabetes-related metabolic damage to the sensory nervous system. It affects more than 3 million Americans and is leading cause of nerve damage-associated pain worldwide. Currently approved drugs such as gabapentin, pregabalin, and duloxetine provide pain relief only in 1 out of 4 or 5 people with DPN, pointing to a great need to identify effective therapy for these patients. Recent literature suggests that certain methods of assessing sensory nerve function in neuropathic pain patients may provide prediction to individual analgesic response; however, no placebo-controlled studies have been performed with the primary goal of identifying treatment response predictors in DPN. We propose in this study to examine whether sensory testing to determine mechanical pain threshold [MPT] or heat pain threshold [HPT] will predict the subject's response to IV lidocaine analgesic therapy. We hypothesize that people with painful DPN who have high MPT or HPT are more likely to respond to lidocaine treatment. This is a prospective, double blind, placebo-controlled study with the primary objective of determining whether the results from the sensory testing predict the response to systemic lidocaine in patients with painful DPN. Consented subjects will attend a screening visit and two intervention visits, during which they will undergo sensory testing and receive intravenous lidocaine or placebo infusion in a cross-over design. At enrollment, each patient will be assigned a study number, which will match a previously prepared computer-generated list of randomization numbers to determine the sequence of interventions: lidocaine and then placebo, or vice versa. An unblinded research nurse coordinator will be assigned to match the study number with randomized treatment sequence, and this person will prepare the study medications, which will look identical. This research nurse coordinator will not be involved at any stage at patient assessment or data analysis. The participants and all other study personnel will be blinded to the treatment allocation.

Official Title
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Predicting Individual Response to Analgesic Treatment in Painful Diabetic Neuropathy

Conditions
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Diabetes, Peripheral Neuropathy, Pain

Intervention / Treatment
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* Drug: lidocaine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18; Diagnosis of Diabetes Mellitus (Fasting Plasma Glucose > 126 mg/dL and/or HbA1C >6.5%); Distal symmetric pain in lower extremities with duration of more than 3 months; Presence of either numbness or at least 1 sensory disturbance (increased or decreased sensitivity) in the feet. Spontaneous pain with intensity of ≥ 4 on 0-10 Numerical Rating Scale (NRS). Exclusion Criteria: Not giving consent to participate in the study; Unable to complete self-report pain questionnaire; History of moderate to severe renal or liver failure; History of other central or peripheral neurologic disorders; History of cardiac arrhythmias; Contraindication to intravenous lidocaine; Pregnancy or lactation.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal saline infusion then lidocaine infusion<br>Intravenous infusion of normal saline over a 40 minute period. second intervention: Intravenous infusion of lidocaine [5mg/kg] over a 40 minute period. | Drug: lidocaine<br>* lidocaine is a sodium channel blocker/analgesic. It is approved for intravenous administration for cardiac arrhythmias.<br>Drug: Placebo<br>* Normal saline, approved for hypovolemia, and homeostasis.<br>|
| Active Comparator: Lidocaine infusion, then normal saline infusion<br>Intravenous infusion of lidocaine [5mg/kg] over a 40 minute period. second intervention: Intravenous infusion of normal saline over a 40 minute period. | Drug: lidocaine<br>* lidocaine is a sodium channel blocker/analgesic. It is approved for intravenous administration for cardiac arrhythmias.<br>Drug: Placebo<br>* Normal saline, approved for hypovolemia, and homeostasis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Spontaneous Pain at 60-120 Minutes After Lidocaine Infusion Initiated (Assessed on 0-10 NRS) | Spontaneous pain will be assessed on numerical rating scale NRS (0= no pain, 10=worst pain imaginable) prior to infusion and then repeatedly for 120 minutes. The outcome measure will use the average of pain intensity measured at timepoints in the 60-120 min range after beginning of infusion. The mean %change in pain (from baseline) will be compared between lidocaine and placebo arms. | Baseline compared to 60-120 minutes after starting the infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evoked Mechanical and Thermal Sensation at Baseline and 60 Minutes After Infusion Initiation. | Thermal and mechanical responses will be assessed at baseline and 60 minutes after infusions. Evoked intensities measured on a 0-10 sensory scale, where 5 is normal sensation, a number lower than 5 is reduced sensation and a number higher than 5 is greater sensation. | - 60 minutes (baseline) and + 60 minutes of initiating infusion | 
| NPSI (Neuropathic Pain Symptom Inventory) Descriptors of Pain at Baseline and 60 Min After Infusion | NPSI pain descriptors will be assessed prior to infusion of placebo and lidocaine (baseline) and again at 60 minutes post-infusion. Descriptors are expressed on a 0-10 scale; 0-minimum (least), and 10 maximum (worst) score. | Baseline to 60 minutes of initiating infusion | 
| Change in Spontaneous Pain Intensity as a Function of Baseline MPT | Correlation between Mechanical Pain Threshold (MPT in mN) at baseline and reduction in spontaneous pain intensity (% reduction on 0-10 NRS) at 60-120 minutes (averaged) from the study drug infusion. The slopes (Pearson coefficients) of the correlation obtained from lidocaine vs. placebo will be compared. | baseline to 60-120 minutes after starting the infusion | 
| Change in Spontaneous Pain Intensity as a Function of Baseline HPT | Correlation between Heat Pain Threshold (HPT in degrees Celsius) at baseline and reduction in spontaneous pain intensity (% reduction on 0-10 NRS) at 60-120 minutes (averaged) from the study drug infusion. The slopes (Pearson coefficients) of the correlation obtained from lidocaine vs. placebo will be compared. | Baseline to 60-120 minutes after starting the infusion |