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

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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:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Bryon Adinoff, University of Texas Southwestern Medical Center

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.

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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

Resource links provided by the National Library of Medicine


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




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.



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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01929343


Locations
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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
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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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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    Key Record Dates
Results First Posted: December 31, 2020
Last Update Posted: December 31, 2020
Last Verified: December 2020

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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:
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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