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Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers

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ClinicalTrials.gov Identifier: NCT03271528
Recruitment Status : Recruiting
First Posted : September 5, 2017
Last Update Posted : August 21, 2018
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Eric Devine, Boston Medical Center

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

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Lacosamide Drug: Placebo oral capsule Phase 1

Detailed Description:
The present proposal is 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 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 are to: 1) test the effects of lacosamide on alcohol self-administration and craving, 2) test the effects of 5 days of lacosamide administration on cognitive function, and 3) test the effects of lacosamide on alcohol consumption and craving during a 8-day period of exposure. The effects of 8-days of locasamide (300mg) or placebo will be evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=28) will be randomized to the order of exposure (lacosamide or placebo) prior to completing two alcohol self-administration trials. Subjects will receive a priming drink of alcohol and will have access to 8 alcoholic drinks over a 2-hour period. The investigators anticipate that subjects will 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 will be 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a double-blind, randomized, placebo-controlled, crossover design trial that will test the effect of lacosamide on alcohol self-administration and craving following a priming dose of alcohol.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This study is double-blind. Medications are over-encapsulated.
Primary Purpose: Treatment
Official Title: Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers
Actual Study Start Date : April 15, 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
Drug Information available for: Lacosamide

Arm Intervention/treatment
Experimental: lacosamide Drug: Lacosamide
Lacosamide titration will be done to a target dose of 300mg. Participants will take 100 mg of lacosamide once on day 1, twice per day from day 2 until day 6, on day 7 the lacrosamide dose will increase to 150 mg twice daily, and on day 8 the participant will take one dose of 150 mg.
Other Name: vimpat

Placebo Comparator: Placebo oral capsule Drug: Placebo oral capsule
Participants will take a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.




Primary Outcome Measures :
  1. Alcohol Consumption [ Time Frame: 4 hours ]
    Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. This outcome will be measured as standard drink units. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.


Secondary Outcome Measures :
  1. Alcohol Cravings [ Time Frame: 4 hours ]
    Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. The Participant marks a point on the line that matches their amount of alcohol craving.

  2. Alcohol Urge [ Time Frame: 4 hours ]
    The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly disagree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Lower scores are associated with less urge for an alcoholic drink.

  3. Verbal Fluency [ Time Frame: 21 days ]
    The Controlled Word Association (COWAT) is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. The participant is asked to name words beginning with a letter, excluding proper nouns, for one minute and this procedure is repeated three times. The most commons letters used are FAS because of their frequency in the English language. The examiner writes down the words provided by the participant on a piece of paper. It usually takes 5-10 minutes. The more words, the subject generates, the better the fluency.

  4. Cognitive function [ Time Frame: 21 days ]
    The Wechsler Adult Intelligence Scale (WAIS-5) Spatial and Digit Span tests will be used to assess subjects' working memory. Subjects will be asked to repeat back an increasing number of digits. Higher scores are indicative of higher levels of working memory and lower scores are indicative of lesser working memory function.

  5. Alcohol craving at titration [ Time Frame: 7 days ]
    The Visual Analog Scale (VAS) will be used to assess alcohol craving during the medication titration period. The VAS is a 10 cm straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. The Participant marks a point on the line that matches their amount of alcohol craving. The point is measured from baseline (mm) to yield a scale score between 0-100.

  6. Cognitive aspects of alcohol craving [ Time Frame: 7 days ]
    The Obsessive-Compulsive Drinking Scale (OCDS) is a quick and reliable 14 item self-rating instrument that provides a total and two subscale scores (obsessive and compulsive) that measure some cognitive aspects of alcohol "craving". Each item is scored from 0 to 4 with lower scores indicating less obsessive or compulsive drinking.



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Ages Eligible for Study:   21 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria

  1. 21-35 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 one episode of binge drinking (>3 for women, >4 for men) in each of the four weeks prior to baseline screening
  5. Meets DSM-5 criteria for mild alcohol use disorder or greater severity.
  6. Have a smartphone to complete some of the study assessments.

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): NCT03271528


Contacts
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Contact: Eric Devine, PhD 617-638-7888 eric.devine@bmc.org

Locations
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United States, Massachusetts
Boston University Psychiatry Research Center, Clinical Studies Unit Recruiting
Boston, Massachusetts, United States, 02118
Contact: Eric G Devine, Ph.D.    617-414-1990    eric.devine@bmc.org   
Sponsors and Collaborators
Boston Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Eric Devine, PhD Assistant Professor

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Responsible Party: Eric Devine, Assistant Professor, Boston Medical Center
ClinicalTrials.gov Identifier: NCT03271528     History of Changes
Other Study ID Numbers: H-36766
1R21AA026389-01 ( U.S. NIH Grant/Contract )
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Eric Devine, Boston Medical Center:
Lacosamide
Alcohol craving
Alcohol Urge Questionnaire
Obsessive-Compulsive Drinking Scale

Additional relevant MeSH terms:
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Alcoholism
Alcoholic Intoxication
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ethanol
Lacosamide
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Anticonvulsants
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action