Clinical trial NCT03271528: Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers
Official title: Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alcohol Use Disorder
Keywords: Lacosamide
Alcohol craving
Alcohol Urge Questionnaire
Obsessive-Compulsive Drinking Scale
Visual Analog Scale
Alcohol consumption
Alcohol use disorder
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2017-09-05
Enrollment: 66
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a double-blind, randomized, placebo-controlled, crossover design trial to test the effect of lacosamide on alcohol self-administration and craving following a priming dose of alcohol.This study is a within subjects design in which each subject receives both study drug (lacosamide) and placebo during participation.
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, placebo-controlled, crossover design trial tested the effect of lacosamide on alcohol self-administration and craving following a priming dose of alcohol. The specific objective of this study was to determine whether lacosamide, a novel anticonvulsant that is FDA-approved for treating partial seizures, has effects on alcohol craving and consumption.

Detailed description: The present proposal was intended to answer the call for accelerating drug development by exploring the potential of a novel anticonvulsant, lacosamide, as a candidate medication for the treatment of alcohol use disorder (AUD). This drug, which is approved for the treatment of seizure disorders, has unique pharmacological actions that include enhancement of slow sodium channel inactivation and inhibition of collapsin response mediator protein-2 (CRMP-2). Alcohol consumption in mice that had knockdown of CRMP-2 within the nucleus accumbens was decreased from levels seen in control animals. In rodent studies, lacosamide administration has produced reductions in 'excessive' drinking and has experimentally-induced decreased expression of the CRMP-2 protein. These findings implicate CRMP-2 as playing a role in the regulation of alcohol consumption. None of the FDA-approved AUD medications or medications commonly used off-label to treat AUD target this CRMP-2 pathway, making lacosamide a promising compound for AUD drug development. The aims of this study were to: 1) test the effects of lacosamide on alcohol self-administration and craving, 2) test the effects of 7 days of lacosamide administration on cognitive function, and 3) test the effects of lacosamide on alcohol consumption and craving during a 7-day period of exposure. The effects of 7 days of lacosamide (300mg) or placebo were evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=27) were randomized to the order of exposure (lacosamide or placebo) prior to completing two alcohol self-administration trials. Subjects received a priming drink of alcohol and had access to 8 alcoholic drinks over a 2-hour period. The investigators anticipated that subjects would consume less alcohol during an alcohol self-administration trial when receiving lacosamide compared to when they are receiving placebo. Significant lacosamide-induced reductions in the quantity of alcohol self-administered are considered to be an indication that this drug may have value as an AUD medication. This study may provide a rationale for phase II clinical studies testing lacosamide with a treatment-seeking AUD population. These results should also help to spur further pre-clinical investigation into the role play by CRMP-2 in regulating both alcohol consumption and alcohol seeking behaviors.

Eligibility criteria: Subject Inclusion Criteria

1. 21-55 years of age
2. Can provide proof of age with state-issued or federal picture ID
3. Exceeds safe weekly drinking limits (≥14 drinks for women or ≥21 drinks for men per week)
4. Reports at least an average of one episode per week of binge drinking (\>3 for women, \>4 for men) in the four weeks prior to baseline screening
5. Meets DSM-5 criteria for mild alcohol use disorder or greater severity.
6. Has a smartphone to complete some of the study assessments.

Subject Exclusion Criteria

1. Currently seeking treatment for alcohol problems
2. Clinical Institute Withdrawal Assessment at \>10
3. DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a substance use disorder other than alcohol, nicotine, marijuana or caffeine
4. If female, pregnant, nursing, or have plans to become pregnant
5. If female, does not agree to use an accepted form of birth control
6. Is currently using medications for which alcohol is a contraindication
7. Has a medical or mental health condition for which further alcohol exposure at the planned dose range would be contraindicated.
8. Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS)
9. Has a history of myocardial infarction, congestive heart failure, has a risk for the development of heart block, or are taking medications that can decrease conduction through the atrial ventricular node.
10. Has previous exposure to lacosamide
11. Has received any form of counseling, self-help, pharmacotherapy, or other intervention to treat AUD in the past 90 days.
12. Is unwilling to suspend use of multivitamins that contain riboflavin during study participation
13. Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, or methamphetamines
14. Liver function values AST or ALT are twice the normal limit
15. GFR \<80 mL/min
16. Unable to comfortably abstain from nicotine for a period of 8 hours.

Primary outcomes:
measure: Alcohol Consumption in Alcohol Self-Administration Trials
timeFrame: 2 hours
Secondary outcomes:
measure: Verbal Fluency: Controlled Word Association (COWAT)
timeFrame: 3 minutes
measure: Cognitive Function: Spatial Span Forward
timeFrame: 10 minutes
measure: Cognitive Function: Spatial Span Backward
timeFrame: 10 minutes
measure: Cognitive Function: Digit Span Forward
timeFrame: 10 minutes
measure: Cognitive Function: Digit Span Backward
timeFrame: 10 minutes
measure: Cognitive Function: Digit Span Sequencing
timeFrame: 10 minutes
measure: Alcohol Craving: Obsessive-Compulsive Drinking Scale (OCDS) Pretrial
timeFrame: 5 minutes
measure: Alcohol Craving: Visual Analog Scale (VAS) Pretrial
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 10
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 20
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 30
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 40
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 30
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 60
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 90
timeFrame: 1 minute
measure: Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 120
timeFrame: 1 minute
measure: Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 30
timeFrame: 1 minute
measure: Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 60
timeFrame: 1 minute
measure: Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 90
timeFrame: 1 minute
measure: Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 120
timeFrame: 1 minute
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston University Psychiatry Research Center, Clinical Studies Unit
state: Massachusetts
Study officials:
affiliation: Assistant Professor
name: Eric Devine, PhD
role: PRINCIPAL_INVESTIGATOR
References: