Neural Correlates of Lidocaine Analgesia (NeuCLA)

The purpose of this study is to characterize the effects of intravenous lidocaine on pain processing and cognitive function. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will consist of 1 visit and involves no long-term follow up.

Study Overview

• Status: Completed
• Conditions: Pain; Anesthesia
• Intervention / Treatment: Device: Peripheral Nerve Stimulation; Drug: Lidocaine IV

Detailed Description

This is an observational cohort study of volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of intravenous lidocaine on pain processing and cognitive function. A steady-state effect-site concentration of lidocaine will be achieved, and a short battery of cognitive behavioral tasks will be employed. At the dose target, pain task functional MRI and resting-state connectivity will be determined. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of intravenous lidocaine, a commonly-used opioid alternative analgesic agent.

Aim1: Determine cognitive behavioral effects of a steady-state dose of IV lidocaine using a short battery of tasks. The investigators hypothesize that the administration of lidocaine will correlate to decreased pain ratings, slowed psychomotor response, and decreased memory encoding.

Aim2: Determine the neural effects of a steady-state dose of IV lidocaine in response to acute pain, and on resting connectivity. The investigators hypothesize that pain task-related activation will decrease in the insula and anterior cingulate, corresponding to decreased ratings of pain intensity and unpleasantness. Additionally, the investigators expect widespread decreases in long-range functional connectivity between brain areas know to be involved in these two areas and other known to be involved in pain processing.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 18 to 70
• Be of normal body-weight
• Be generally healthy
• Have none of the specific exclusion criteria
• Have a valid email address and phone number throughout the study

Exclusion Criteria:

• Pregnancy
• Body mass index > 40
• Having moderate to severe sleep apnea
• Having chronic pain requiring the regular use of pain medicine 3 or more times per week
• Having neurologic or psychiatric disease, including benign tremor, anxiety, and depression
• Having a history of seizures
• Having history of cardiac rhythm disturbance (such as heart block, or atrial fibrillation)
• Being severely claustrophobic
• Having metal implants or non-removable metal piercings
• Having metal-containing tattoos, particularly on the face
• Having a history of adverse reaction to lidocaine
• Are regularly taking: antiepileptics, antidepressants, anti-psychotics, anti-anxiety medication, stimulants, sleep-aids, or pain medication
• Are taking prescribed medications for psychiatric or neurological conditions
• Having hypersensitivity to lidocaine or to any other local anesthetics of the amide type
• Having Wolff-Parkinson-White syndrome
• Having known renal or hepatic dysfunction
• having glucose-6-phosphate dehydrogenase deficiency or history of methemoglobinemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine; Subjects will receive lidocaine during the drug portion of the experiment.	Device: Peripheral Nerve Stimulation; Experimental acute pain stimulus will be delivered using an electric nerve stimulator.; Other Names: Electric Nerve Stimulation; Drug: Lidocaine IV; Subjects will receive an intravenous infusion of lidocaine for about 30 minutes.; Other Names: Xylocaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition	The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Primary outcome is listed for the Right insula, but similar scores are calculated throughout the brain. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate stronger correlation between functional MRI signal change and the task timing, with positive values indicating increases in fMRI signal and negative Z-scores indicating decreases. Practically, higher positive Z-scores indicate increased brain activity and larger negative Z-scores indicate decreased brain activity. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.	4.5 minutes
Resting-state Functional Connectivity Difference: Drug-free Minus Lidocaine	Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between drug-free and lidocaine conditions. The reported value is the FC change between the right insula and anterior cingulate. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the drug-free condition, and more negative scores mean stronger connectivity with lidocaine. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.	8 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity Score Difference, Drug-free Condition Minus Lidocaine Condition	Numerical rating scale (0-10) pain score difference, comparing drug-free to the steady-state dose of lidocaine. Higher pain scores indicate more pain; a positive difference between pain score during the drug-free condition minus the value during the lidocaine condition indicates pain reduction (a better outcome).	12 minutes
Memory Performance Difference, Drug-free Minus Lidocaine Condition	Performance on a short computer-based test of memory for visual pictures will be quantified using signal detection metric d-prime, reflecting ability (in standard deviation units) to detect previously-seen images from the background "noise" of previously un-seen images. Differences will be determined between the drug-free condition and the lidocaine condition. Higher values of d-prime indicate stronger memory performance; a positive difference for drug-free minus lidocaine condition would indicate the expected decrease in memory performance.	3 minutes
Motor Response Time Differences	Response times (in ms) after hearing a tone will be recorded and compared between the drug-free and Lidocaine condition, with the calculated difference in response times reported. Higher values will reflect slower responses, which are expected under the lidocaine condition.	1 minute

Collaborators and Investigators

• Sponsor: Keith M Vogt
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Keith M Vogt, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: lidocaine; functional MRI; functional connectivity; electric nerve stimulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Lidocaine
• Other Study ID Numbers: STUDY21120115; R35GM146822 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No