Cocaine AddictionPhase 2LIDONCT01929343
Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
A Phase 2 study testing lidocaine following cue-induced craving, lidocaine following neutral stimulus and saline in people with Cocaine Addiction, run by Bryon Adinoff at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 60 years
- Conditions the study is for
- Cocaine Addiction
- What is being tested?
- lidocaine following cue-induced craving, lidocaine following neutral stimulus and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 25-60 years old
- men or women
- any race or ethnicity
- cocaine addition is primary present and lifetime drug of abuse
- live locally
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UT Southwestern Medical Center at Dallas, Division on Addictions
Dallas, Texas, 75390-8564
About this study
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.
Read the 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.
- Conditions
- Cocaine Addiction
- Being tested
- lidocaine following cue-induced craving, lidocaine following neutral stimulus, saline
- Keywords
- cocaine, addiction, lidocaine, memory, drug abuse
- Medical subject headings
- Cocaine-Related Disorders, Behavior, Addictive, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lidocaine following cue-induced cravingDrug
Also called Xylocaine
as described in Arm Description
lidocaine following neutral stimulusDrug
Also called Xylocaine
as described in Arm Description
salineDrug
Also called 0.9% Sodium chloride
as described in Arm Description
| Study group | Role | What they receive |
|---|---|---|
| lidocaine following cue-induced craving | Experimental | 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. Receives: Drug: lidocaine following cue-induced craving |
| lidocaine following neutral stimulus | Active comparator | 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. Receives: Drug: lidocaine following neutral stimulus |
| saline | Placebo comparator | Saline will be administered at same volume of lidocaine in active arms. Receives: Drug: saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cue-induced Craving After Lidocaine/Saline Administration.
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.
Measured: craving measured immediately following reading of the script.
Physiological Responses as Measured by Heart Rate After Lidocaine/Saline Administration.
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.
Measured: 120 seconds, during reading of the script.
Physiological Responses as Measured by Blood Pressure After Lidocaine/Saline Administration.
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.
Measured: BP will measured during the two minutes of script reading.
Physiological Responses as Measured by Galvanic Skin Response (GSR) After Lidocaine/Saline Administration.
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.
Measured: 2 minutes during script reading.
Physiological Responses as Measured by EMG (Electromyography) After Lidocaine/Saline Administration.
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.
Measured: 2 minutes during administration of script.
Secondary outcomes (2)
Cocaine Use
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.
Measured: cocaine use will be measure during the 4 weeks following infusion
Cocaine Craving
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.
Measured: cocaine craving will be measure during the 4 weeks following infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2013 (estimated)
- Study startJan 2014
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cocaine AddictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bryon Adinoff
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor-investigator, Bryon Adinoff, University of Texas Southwestern Medical Center
- Investigators
- Bryon Adinoff, MD, Principal investigator, UT Southwestern Medical Center, VA North Texas Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01929343
- Sponsor's protocol ID
- STU 032013-049
- Acronym
- LIDO
- Status last verified
- Dec 2020
- First submitted
- 22 Aug 2013
- Last updated
- 31 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32480252
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
- ClinicalTrials.gov ID
- NCT01929343
- Acronym / sponsor ID
- LIDO / STU 032013-049
- Conditions
- Cocaine Addiction
- Keywords
- cocaine, addiction, lidocaine, memory, drug abuse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Bryon AdinoffUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jan 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 27 Aug 2013 (estimated)
- Results
- Posted 31 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| lidocaine following cue-induced craving | Experimental | Drug: lidocaine following cue-induced cravingLidocaine 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. |
| lidocaine following neutral stimulus | Active comparator | Drug: lidocaine following neutral stimulusLidocaine 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. |
| saline | Placebo comparator | Drug: salineSaline will be administered at same volume of lidocaine in active arms. |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 25-60 years old
- men or women
- any race or ethnicity
- cocaine addition is primary present and lifetime drug of abuse
- live locally
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lidocaine following cue-induced cravingAlso: Xylocaineas described in Arm Description | Drug | lidocaine following cue-induced craving |
| lidocaine following neutral stimulusAlso: Xylocaineas described in Arm Description | Drug | lidocaine following neutral stimulus |
| salineAlso: 0.9% Sodium chlorideas described in Arm Description | Drug | saline |
Primary outcome
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.
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.
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.
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.
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.
2 secondary outcomes
Cocaine Use
Time frame: cocaine use will be measure during the 4 weeks following infusion
Cocaine Craving
Time frame: cocaine craving will be measure during the 4 weeks following infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32480252Becker 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryon Adinoff, MD principal investigator
UT Southwestern Medical Center, VA North Texas Health Care System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lidocaine following cue-induced craving, lidocaine following neutral stimulus and saline in people with Cocaine Addiction, run by Bryon Adinoff at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cue-induced Craving After Lidocaine/Saline Administration. (time frame: craving measured immediately following reading of the script.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01929343, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2020.