Pilot Human Lab Study of Lacosamide in Alcohol Use Disorder (AUD)

Study Overview
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Brief Summary
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The overall goal of the proposed project is to improve the treatment of individuals with AUD. The investigators will conduct the first pilot human laboratory study to assess the effects of two doses of lacosamide on alcohol drinking and craving. The investigators will assess its effects on reducing alcohol intake using a human laboratory method, the Yale Alcohol Drinking Paradigm (ADP). The investigators will also assess the feasibility of the Alcohol Drinking Paradigm (ADP) in order to position our research team to have the capacity to conduct future, larger, hypothesis-testing human laboratory-based experiments designed to test the efficacy of potential alcohol treatments.

Detailed Description
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Four heavy-drinking non-treatment seeking male community volunteers with a diagnosis of AUD will undergo 3 ADP sessions. In each of the 3 ADP sessions, they will receive one of the following 3 different interventions: either 100 mg of lacosamide, 200 mg of lacosamide or placebo. The ADP session is a one day human laboratory session at the SFVA Medical Center. This human laboratory session involves the self-administration of alcoholic beverages by research participants under highly structured, observed conditions in order to evaluate the effects of the study drug interventions (either 100 mg lacosamide, 200 mg lacosamide, or placebo) on alcohol craving and alcohol consumption. The study follows a double-blind placebo-controlled crossover design in which each participant receives each of the 3 drug interventions in a randomly assigned sequence. There were 4 possible sequences representing the 4 arms of the study.

Official Title
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A Pilot Placebo-controlled Human Laboratory Feasibility Study of Lacosamide Effects in Alcohol Use Disorder

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Lacosamide 100 mg
* Drug: Lacosamide 200 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men, ages 21-50; Able to read English and to complete study evaluations; Meet DSM-V criteria for current alcohol use disorder (AUD); Average weekly alcohol use of 25-70 standard drinks for men over the past 30 days; No more than 3 days/week of alcohol abstinence in the past 30 days, to maximize likelihood that participants will choose to drink during the laboratory sessions. Exclusion Criteria: Individuals who are seeking AUD treatment or have been in treatment within the past 6 months; Current DSM-V non-alcohol use disorder other than tobacco or cannabis; Positive urine drug test results at more than one baseline appointment for opioids, cocaine, benzodiazepines or barbiturates; Regular use of psychoactive drugs including antipsychotics, anxiolytics and antidepressants during the 30 days prior to entry, as well as anticonvulsants, beta blockers, central nervous system stimulants or depressants, or other drugs that cause excessive sedation; Taking medications that may interact with lacosamide, e.g. medications that prolong the ECG PR interval, or medications with strong CYP3A4 and CYP2C9; Psychosis or any other serious mental illness as judged by SCID and study physician assessment; Medical conditions that in the judgment of the study physician contraindicate the consumption of alcohol; Medical conditions that in the judgment of the study physician contraindicate LAC (non contraindications listed in the FDA-approved Prescribing Information for LAC); Any other medical conditions that in the opinion of the study physician would make study participation hazardous; History of serious alcohol withdrawal (e.g. seizures, DTs, hospitalization) or a Clinical Institute Withdrawal Assessment Scale (CIWA-AD) score greater than or equal to 8; Participants who report disliking spirits will be excluded because 80 proof liquor will be provided during the alcohol self-administration periods; Participants who have taken any investigational drug within 4 weeks preceding study entry; Participants with first-degree atrioventricular block (AV block), PR interval lengthened beyond 0.20 seconds or greater.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover Sequence A: Placebo, then Lacosamide 200 mg, then Lacosamide 100 mg<br>Participants receive a single dose of Placebo in ADP Session 1. After a 1 week washout period, they undergo ADP Session 2 in which they receive a single dose of Lacosamide 200 mg. After another 1 week washout period, they undergo ADP Session 3 in which they receive a single dose of Lacosamide 100 mg. | Drug: Placebo<br>* Oral medication<br>* Other names: Placebo capsule identical in appearance to Lacosamide 100 mg and 200 mg capsules.;Drug: Lacosamide 100 mg<br>* Oral medication<br>* Other names: Lacosamide 100 mg capsule identical in appearance to Placebo and Lacosamide 200 mg capsule;Drug: Lacosamide 200 mg<br>* Oral medication<br>* Other names: Lacosamide 200 mg capsule identical in appearance to Placebo and Lacosamide 100 mg capsules.;|
| Experimental: Crossover Sequence B: Lacosamide 200 mg, then Lacosamide 100 mg, then Placebo<br>Participants receive a single dose of Lacosamide 200 mg in ADP Session 1. After a 1 week washout period, they undergo ADP Session 2 in which they receive a single dose of Lacosamide 100 mg. After another 1 week washout period, they undergo ADP Session 3 in which they receive a single dose of Placebo. | Drug: Placebo<br>* Oral medication<br>* Other names: Placebo capsule identical in appearance to Lacosamide 100 mg and 200 mg capsules.;Drug: Lacosamide 100 mg<br>* Oral medication<br>* Other names: Lacosamide 100 mg capsule identical in appearance to Placebo and Lacosamide 200 mg capsule;Drug: Lacosamide 200 mg<br>* Oral medication<br>* Other names: Lacosamide 200 mg capsule identical in appearance to Placebo and Lacosamide 100 mg capsules.;|
| Experimental: Crossover Sequence C: Lacosamide 200 mg, then Placebo, then Lacosamide 100 mg<br>Participants receive a single dose of Lacosamide 200 mg in ADP Session 1. After a 1 week washout period, they undergo ADP Session 2 in which they receive a single dose of Placebo. After another 1 week washout period, they undergo ADP Session 3 in which they receive a single dose of Lacosamide 100 mg. | Drug: Placebo<br>* Oral medication<br>* Other names: Placebo capsule identical in appearance to Lacosamide 100 mg and 200 mg capsules.;Drug: Lacosamide 100 mg<br>* Oral medication<br>* Other names: Lacosamide 100 mg capsule identical in appearance to Placebo and Lacosamide 200 mg capsule;Drug: Lacosamide 200 mg<br>* Oral medication<br>* Other names: Lacosamide 200 mg capsule identical in appearance to Placebo and Lacosamide 100 mg capsules.;|
| Experimental: Crossover Sequence D: Lacosamide 100 mg, then Lacosamide 200 mg, then Placebo<br>Participants receives a single dose of Lacosamide 100 mg in ADP Session 1. After a 1 week washout period, they undergo ADP Session 2 in which they receive a single dose of Lacosamide 200 mg. After another 1 week washout period, they undergo ADP Session 3 in which they receive a single dose of Placebo. | Drug: Placebo<br>* Oral medication<br>* Other names: Placebo capsule identical in appearance to Lacosamide 100 mg and 200 mg capsules.;Drug: Lacosamide 100 mg<br>* Oral medication<br>* Other names: Lacosamide 100 mg capsule identical in appearance to Placebo and Lacosamide 200 mg capsule;Drug: Lacosamide 200 mg<br>* Oral medication<br>* Other names: Lacosamide 200 mg capsule identical in appearance to Placebo and Lacosamide 100 mg capsules.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment Feasibility (Time, in Months,) Required to Recruit, Screen and Conduct the Study Procedures | Recruitment feasibility will be measured as the time (in months) required to recruit, screen and conduct the study procedures for a total of 4 participants. | 7 months | 
| Retention Feasibility (Proportion of Participants Completing the Alcohol Drinking Paradigm (ADP) Sessions) | Retention feasibility will be measured by the proportion of participants completing the Alcohol Drinking Paradigm (ADP) Sessions 1, 2 and 3. | 6.5 weeks | 
| Tolerability (Number of Participants With Mild, Moderate, or Severe Adverse Events) | Tolerability will be measured by the number of participants with mild, moderate, and severe adverse events for each of the 3 drug interventions (100 mg lacosamide, 200 mg lacosamide and placebo). | 3 days (1 day each for ADP Session 1, 2, and 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Craving | Alcohol craving will be measured during Alcohol Drinking Paradigm (ADP) sessions 1, 2 and 3 using the total score of the Alcohol Urge Questionnaire (AUQ). The AUQ has 8 items. Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7; items 2 and 7 are reverse scored). Higher scores reflect greater craving. Total score range is from a minimum of 8 to a maximum of 56. The AUQ is administered before study medication and at various times after study medication. The AUQ score reported here is the highest AUQ score following administration of study medication. | 3 days (1 day each for ADP Session 1, 2, and 3. Each ADP Session included 1 dose of the drug intervention, either Placebo, Lacosamide 100 mg, or Lacosamide 200 mg). | 
| Alcohol Consumption (Number of Standard Drinks Consumed) | Alcohol consumption is measured during each of the Alcohol Drinking Paradigm (ADP) sessions, 1, 2 and 3. In each session participants received one of the 3 drug interventions, Placebo, Lacosamide 100 mg, or Lacosamide 200 mg. Consumption was measured using the number of alcoholic standard drinks consumed during the ADP sessions. A standard drink per NIAAA definition is 14 grams of pure alcohol. | 3 days (1 day each for ADP Session 1, 2, and 3. Each ADP Session included 1 dose of the drug intervention, either Placebo, Lacosamide 100 mg, or Lacosamide 200 mg). | 
| Subjective Effects of Alcohol Consumption | Subjective effects of alcohol consumption are measured during the Alcohol Drinking Paradigm (ADP) sessions 1, 2 and 3 using the Biphasic Alcohol Effects Scale (BAES), which has 2 subscales; the Stimulation Subscale range is 0 - 70, where 0 is the least and 70 is the greatest stimulation; the Sedation Subscale range is 0 - 70, where 0 is the least and 70 is the greatest sedation. The BAES was administered both before and at various timepoints after study medication administration in each of the ADP sessions. The BAES scores reported here are the peak Stimulation scores after medication administration and peak Sedation scores after medication administration for each of ADP sessions 1, 2 and 3. | 3 days (1 day each for ADP Session 1, 2, and 3. Each ADP Session included 1 dose of the drug intervention, either Placebo, Lacosamide 100 mg, or Lacosamide 200 mg). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol craving, human laboratory, lacosamide, non-treatment seeking