Lidocaine for Diabetic Peripheral Neuropathy

Predicting Individual Response to Analgesic Treatment in Painful Diabetic Neuropathy

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.

Study Overview

• Status: Completed
• Conditions: Pain; Diabetes; Peripheral Neuropathy
• Intervention / Treatment: Drug: lidocaine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine/Barnes Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18;
2. Diagnosis of Diabetes Mellitus (Fasting Plasma Glucose > 126 mg/dL and/or HbA1C >6.5%);
3. Distal symmetric pain in lower extremities with duration of more than 3 months;
4. Presence of either numbness or at least 1 sensory disturbance (increased or decreased sensitivity) in the feet.
5. Spontaneous pain with intensity of ≥ 4 on 0-10 Numerical Rating Scale (NRS).

Exclusion Criteria:

1. Not giving consent to participate in the study;
2. Unable to complete self-report pain questionnaire;
3. History of moderate to severe renal or liver failure;
4. History of other central or peripheral neurologic disorders;
5. History of cardiac arrhythmias;
6. Contraindication to intravenous lidocaine;
7. Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Normal saline infusion then lidocaine infusion; 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; lidocaine is a sodium channel blocker/analgesic. It is approved for intravenous administration for cardiac arrhythmias.; Drug: Placebo; Normal saline, approved for hypovolemia, and homeostasis.
ACTIVE_COMPARATOR: Lidocaine infusion, then normal saline infusion; 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; lidocaine is a sodium channel blocker/analgesic. It is approved for intravenous administration for cardiac arrhythmias.; Drug: Placebo; Normal saline, approved for hypovolemia, and homeostasis.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Simon Haroutounian, PhD, Department of Anesthesiology, WUSTL

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2015
• Primary Completion (ACTUAL): October 17, 2018
• Study Completion (ACTUAL): October 17, 2018

Study Registration Dates

• First Submitted: February 3, 2015
• First Submitted That Met QC Criteria: February 9, 2015
• First Posted (ESTIMATE): February 16, 2015

Study Record Updates

• Last Update Posted (ACTUAL): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 201412073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO