Clinical trial NCT01929343: Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
Official title: Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Addiction
Keywords: cocaine
addiction
lidocaine
memory
drug abuse
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2013-08-27
Enrollment: 84
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We propose that the systemic administration of lidocaine following the induction of cue-induced craving, relative to saline plus cue-induced craving or lidocaine without cue-induced craving, will block the reconsolidation of cue memories. This will lead to a reduction in cue-induced craving upon repeated testing as well as subsequent cocaine use and basal craving.

Detailed description: Cocaine dependence is among the most tenacious of the substance use disorders yet remains one of the few lacking an effective pharmacological intervention. As other pharmacologic approaches have not been fruitful, new targets are required. A novel treatment approach is to disrupt the neural processes involved in cue-related memories (memory links between the external stimuli associated with drug use and the subjective drug effect). These engrained memories, when reactivated by cues, elicit craving and a return to drug use. Each cue re-exposure, however, requires the re-remembering (or reconsolidation) of the drug cue. Key molecular processes required for memory reconsolidation are NMDA (N-methyl-D-aspartate) receptor activation, the induction of nitric oxide (NO) synthesis and increased extracellular signal-regulated kinase (ERK) activity. In rodent models, blocking these processes changes the cue-related memory; the cue loses its potency to induce a return to drug self-administration. Lidocaine is an FDA (Food and Drug Administration) approved medication that inhibits activation of NMDA (N-methyl-D-aspartate) receptors and suppresses production of NO (nitric oxide) and ERK (extracellular signal-regulated kinase). Lidocaine, like cocaine, is a local anesthetic with potent effects as a sodium-channel blocker. Unlike cocaine, lidocaine is essentially devoid of activity at monoamine re-uptake transporters and has no rewarding or addictive properties. As lidocaine suppresses the molecular processes required for drug cue reconsolidation and has relatively specific effects upon the striatal regions necessary for drug cue reconsolidation, lidocaine may offer a novel approach for interfering with memory reconsolidation. Two other (Sodium) Na+ channel blockers have also decrease craving and/or substance use in substance-dependent subjects. We propose that the systemic administration of lidocaine following the induction of cue-induced craving, relative to saline plus cue-induced craving or lidocaine without cue-induced craving, will block the reconsolidation of cue memories. This will lead to a reduction in cue-induced craving upon repeated testing as well as subsequent cocaine use and basal craving. If our hypotheses are proven correct, these findings will 1) support a role for lidocaine in cocaine addiction treatment, 2) demonstrate the feasibility and efficacy of attenuating cue-induced memories, and 3) guide the development of a larger study with lidocaine.

Eligibility criteria: Inclusion Criteria:

* 25-60 years old
* men or women
* any race or ethnicity
* cocaine addition is primary present and lifetime drug of abuse
* live locally

Exclusion Criteria:

* Patients with active DSM (Diagnostic Statistical Manual)-IV other Substance Dependence (except nicotine) within the previous three months, Affective Disorder, Schizophrenic Disorders.
* significant cognitive impairment (WTAR\<70) (Wechsler Test of Adult Reading \<70)..
* use of tricyclic anti-depressants, benzodiazepines, cimetidine, mood stabilizers, opioids, lithium, sympathomimetics, anticonvulsants, sedative/hypnotics, β-blockers, or dopamine agonists will be excluded from the study.
* Medical conditions that might limit cooperation (e.g. dementia) or put the patient at medical risk (i.e. significant hematologic, hepatic, renal, or cardiovascular pathology - particularly arrhythmias) will be excluded.
* Patients with congenital or idiopathic methemoglobinemia or patients taking medications associated with increased risk of methemoglobinemia (including sulfonamides, acetaminophen, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, paraaminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine) will be excluded.
* Patients with past or present neurologic disorders (i.e. severe head trauma, transient ischemic attacks, stroke, tumor, etc.) will be excluded. - Active suicidal ideation, pregnant or nursing women, and prisoners will be excluded from the study.

Primary outcomes:
measure: Cue-induced Craving After Lidocaine/Saline Administration.
timeFrame: craving measured immediately following reading of the script.
measure: Physiological Responses as Measured by Heart Rate After Lidocaine/Saline Administration.
timeFrame: 120 seconds, during reading of the script.
measure: Physiological Responses as Measured by Blood Pressure After Lidocaine/Saline Administration.
timeFrame: BP will measured during the two minutes of script reading.
measure: Physiological Responses as Measured by Galvanic Skin Response (GSR) After Lidocaine/Saline Administration.
timeFrame: 2 minutes during script reading.
measure: Physiological Responses as Measured by EMG (Electromyography) After Lidocaine/Saline Administration.
timeFrame: 2 minutes during administration of script.
Secondary outcomes:
measure: Cocaine Use
timeFrame: cocaine use will be measure during the 4 weeks following infusion
measure: Cocaine Craving
timeFrame: cocaine craving will be measure during the 4 weeks following infusion
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas, Division on Addictions
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center, VA North Texas Health Care System
name: Bryon Adinoff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Becker JE, Price JL, Leonard D, Suris A, Kandil E, Shaw M, Kroener S, Brown ES, Adinoff B. The Efficacy of Lidocaine in Disrupting Cocaine Cue-Induced Memory Reconsolidation. Drug Alcohol Depend. 2020 Jul 1;212:108062. doi: 10.1016/j.drugalcdep.2020.108062. Epub 2020 May 12.