Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers

NCT ID: NCT03271528

Last Updated: 2021-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-15
• Study Completion Date: 2020-08-31

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.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lacosamide

Lacosamide titration was done to a target dose of 300mg. Participants took 100 mg of lacosamide once on day 1, 100 mg twice per day from day 2 through day 6 (200 mg daily total), on day 7 the lacosamide dose was increased to 150 mg twice daily (300 mg daily total), and on day 8 the participant took one dose of 150 mg.

Group Type: EXPERIMENTAL

Lacosamide

Intervention Type: DRUG

Lacosamide titration was done to a target dose of 300mg. Participants took 100 mg of lacosamide once on day 1, 100 mg twice per day from day 2 through day 6 (200 mg daily total), on day 7 the lacosamide dose was increased to 150 mg twice daily (300 mg daily total), and on day 8 the participant took one dose of 150 mg.

Placebo oral capsule

Participants took a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Participants took a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.

Interventions

Lacosamide

Lacosamide titration was done to a target dose of 300mg. Participants took 100 mg of lacosamide once on day 1, 100 mg twice per day from day 2 through day 6 (200 mg daily total), on day 7 the lacosamide dose was increased to 150 mg twice daily (300 mg daily total), and on day 8 the participant took one dose of 150 mg.

Intervention Type: DRUG

Placebo oral capsule

Participants took a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.

Intervention Type: DRUG

Other Intervention Names

Vimpat

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Devine, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor

Locations

Boston University Psychiatry Research Center, Clinical Studies Unit

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21AA026389-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-36766

Identifier Type: -

Identifier Source: org_study_id