Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving (LIDO)

• ClinicalTrials.gov Identifier: NCT01929343
• Recruitment Status: Completed
• First Posted: August 27, 2013
• Results First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Sponsor: Bryon Adinoff
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Bryon Adinoff, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cocaine Addiction	Drug: lidocaine following cue-induced craving; Drug: lidocaine following neutral stimulus; Drug: saline	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
• Study Start Date: January 2014
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: lidocaine following cue-induced craving; Lidocaine will be administered immediately following craving induction. Lidocaine will administered at a loading dose of 2mg/kg(milligrams per kilogram) initial bolus over 5 minutes lidocaine followed by continuous infusion at 2mg/kg /hour for 4 hours.	Drug: lidocaine following cue-induced craving; as described in Arm Description; Other Name: Xylocaine
Active Comparator: lidocaine following neutral stimulus; Lidocaine will be administered immediately following neutral stimulus. Lidocaine will administered at a loading dose of 2mg/kg initial bolus over 5 minutes lidocaine followed by continuous infusion at 2mg/kg /hour for 4 hours.	Drug: lidocaine following neutral stimulus; as described in Arm Description; Other Name: Xylocaine
Placebo Comparator: saline; Saline will be administered at same volume of lidocaine in active arms.	Drug: saline; as described in Arm Description; Other Name: 0.9% Sodium chloride

Outcome Measures

Primary Outcome Measures :

1. Cue-induced Craving After Lidocaine/Saline Administration. [ Time Frame: craving measured immediately following reading of the script. ]
   7 days after lidocaine/saline administration, cocaine craving will be measured during the administration of relaxation or craving script. Craving intensity will be measured by the subjective intensity of craving as reported by the participant. Measured via a visual analog scale based on 4 (out of 10) questions from the Cocaine Craving Questionnaire (1-strongly disagree to 7- strongly agree). Highest total score possible 28, lowest score possible is 4. If the score is low in the lidocaine group and high in the saline group, it would mean that lidocaine has successfully decreased the craving response relative to saline.
2. Physiological Responses as Measured by Heart Rate After Lidocaine/Saline Administration. [ Time Frame: 120 seconds, during reading of the script. ]
   7 days after lidocaine/saline administration, heart rate will be measured during the administration of a relaxation or craving script. Heart rate will be measured in beats per minute.
3. Physiological Responses as Measured by Blood Pressure After Lidocaine/Saline Administration. [ Time Frame: BP will measured during the two minutes of script reading. ]
   7 days after lidocaine/saline administration, blood pressure (BP) response will be assessed during relaxation or craving script. Blood pressure will be measured by mmHg.
4. Physiological Responses as Measured by Galvanic Skin Response (GSR) After Lidocaine/Saline Administration. [ Time Frame: 2 minutes during script reading. ]
   7 days after lidocaine/saline administration, GSR will be measured during the reading of the relaxation or saline script. It is predicted that higher GSR would be associated with higher cocaine craving and lower GSR will be associated with lower cocaine craving.
5. Physiological Responses as Measured by EMG (Electromyography) After Lidocaine/Saline Administration. [ Time Frame: 2 minutes during administration of script. ]
   Electromyography (frontal) will be measured during the administration of the relaxation or craving script seven days after infusion. EMG is assessed by uV (microvolts). Higher scores reflect greater amounts of EMG activity, lower scores reflect lower amounts of EMG activity. It was expected that EMG would be positively associated with cocaine craving.

Secondary Outcome Measures :

1. Cocaine Use [ Time Frame: cocaine use will be measure during the 4 weeks following infusion ]
   cocaine use will be measured by urine drug screen and participant self-report three times weekly after lidocaine/saline administration. Cocaine use will be assessed as positive (1) or negative (0) using urine drug screen for cocaine and/or by participant self-report of cocaine use.
2. Cocaine Craving [ Time Frame: cocaine craving will be measure during the 4 weeks following infusion ]
   basal measures of cocaine craving will be measured by Cocaine Craving Questionnaire (CCQ) times weekly after lidocaine/saline administration. The higher the score the more craving and lower the score the less craving. The CCQ has 10 items, each item scored 1-7. Maximum score is 70, minimum score is 7.

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Texas

UT Southwestern Medical Center at Dallas, Division on Addictions

Dallas, Texas, United States, 75390-8564

Sponsors and Collaborators

Bryon Adinoff

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Bryon Adinoff, MD; UT Southwestern Medical Center, VA North Texas Health Care System

  Study Documents (Full-Text)

Documents provided by Bryon Adinoff, University of Texas Southwestern Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] May 21, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bryon Adinoff, Clinical Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01929343
• Other Study ID Numbers: STU 032013-049
• First Posted: August 27, 2013
• Results First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bryon Adinoff, University of Texas Southwestern Medical Center:

cocaine; addiction; lidocaine; memory; drug abuse

Additional relevant MeSH terms:

Cocaine-Related Disorders; Behavior, Addictive; Compulsive Behavior; Impulsive Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Lidocaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action