Enhancing the Effects of Alcohol Treatment With Lamotrigine

Proof-of-Concept Clinical Trial of Lamotrigine as a Candidate Pharmacotherapy for Adolescent Alcohol Use Disorder

This study will help determine the tolerability and efficacy of the mood-stabilizing anticonvulsant lamotrigine in youth with alcohol use disorder. It will also help establish whether and how lamotrigine improves outcomes related to alcohol use. The results of this proof-of-concept study will inform whether a future larger clinical trial is warranted.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Lamotrigine; Drug: Placebo

Detailed Description

Adolescent alcohol use is a leading public health concern worldwide. Clinical trials have tested a variety of psychosocial interventions with youth that yield only modest short-term benefits. One potential way to improve treatments is to augment psychosocial interventions with pharmacotherapy. The National Institutes of Health has mounted a concerted effort to identify medications that reduce drinking for nearly three decades. Although this effort improved treatment for adults, no medication is indicated for adolescent use and randomized controlled trials with teenagers are almost nonexistent. This gap raises key questions about whether and how medications could benefit youth. Optimizing treatment options for youth requires closing this important gap. Lamotrigine is safe with adolescents and does not adversely interact with alcohol. Lamotrigine targets brain mechanisms implicated in alcohol use disorder, and it has shown to help treat adults with alcohol problems. Yet, despite its widespread use with children and adolescents, no published double-blind, placebo-controlled studies have examined the effects of lamotrigine on drinking-related behavior in youth. The purpose of this study is to determine how well teenagers accept lamotrigine plus alcohol education to reduce adolescent alcohol use. This study will also tell us whether teenagers' alcohol use, craving, and enjoyment of drinking are reduced by lamotrigine.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robert Miranda, PhD; Phone Number: (401) 863-6658; Email: Robert_Miranda_Jr@brown.edu
• Study Contact Backup: Name: Hayley Treloar Padovano, PhD; Phone Number: (401) 863-6623; Email: Hayley_Treloar@brown.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Brown University Center for Alcohol and Addiction Studies
      • Contact: Robert Miranda, PhD; Phone Number: 401-863-6658; Email: Robert_Miranda_Jr@brown.edu
      • Contact: Brianna Parlette, MS; Phone Number: 401 863-6687; Email: Brianna_Parlette@brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 16 to 19 years old, inclusive
• Self-reports consuming alcohol ≥ 2 days/week on average in the past 90 days of which ≥ 5 days involved ≥ 4 drinks within a 2-hr period (i.e., binge drinking) for boys and ≥ 3 drinks for girls
• Meet the DSM-5 criteria for alcohol use disorder (AUD)
• Be interested in reducing alcohol use
• Be able to read simple English
• Females taking estrogen-containing oral contraceptives have to agree to use secondary methods of birth control, such as condoms because lamotrigine lowers the effectiveness of estrogen-containing oral contraceptives. Sexually active females cannot be in this study if they do not agree to use a barrier method of birth control (condom) every time they engage in sexual intercourse.

Exclusion Criteria:

• Currently receiving formal AUD treatment
• Significant alcohol withdrawal symptoms
• Coexisting moderate or severe substance use disorder other than cannabis and nicotine, as defined by DSM-5 criteria.
• Positive urine toxicology screen any substances other than cannabis (THC)
• Currently taking a pharmacotherapy for AUD, a carbonic anhydrase inhibitor, or a glucuronidation
• Compelled to alcohol treatment by the justice system or has probation or parole requirements that might interfere with study participation
• History of rash that was serious, required hospitalization, or related to lamotrigine
• Have a history of any serious, unstable medical illness including seizures or hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease
• Clinically significant abnormal liver function tests, including elevation of liver enzymes (AST, ALT) 3-fold above the upper limit of normal.
• Abnormal BUN and creatinine for renal impairment
• Renal or hepatic impairment
• Clinically significant abnormalities per physical exam, hematological assessment, bilirubin concentration, or urinalysis
• Pregnant, nursing, or refusing to use a condom, if female.
• Used psychotropic or anticonvulsant medication (prescribed by a health care professional) in the past 30 days (e.g., topiramate)
• Taking medications contraindicated with lamotrigine (e.g., valproate acid [Depakote], carbamazepine, phenytoin, phenobarbital, primidone, and rifampin, protease inhibitors lopinavir/ritonavir and atazanavir/lopinavi
• History of prior treatment with lamotrigine
• Known sensitivity or allergy to lamotrigine
• A previous history of drug reaction with eosinophilia and systemic symptoms (DRESS) or blood dyscrasias
• A history of Steven-Johnson syndrome or any presentation of symptoms suggestive of Steven-Johnson syndrome.
• Current or lifetime history of psychosis or suicidality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lamotrigine; Lamotrigine (25 mg/day to 200 mg/day in two divided doses) for 9 weeks	Drug: Lamotrigine; Participants will be randomized to lamotrigine (25 mg/day to 200 mg/day in two divided doses) for 9 weeks. A comparator group will receive placebo (sugar pills).; Other Names: Lamictal
Placebo Comparator: Placebo; Identical matching placebo capsules	Drug: Placebo; Matching placebo (sugar pill)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion rates	Percentage of youth who complete the active medication phase will determine feasibility.	9-week active treatment phase
Acceptability of the study medication	Study withdrawal and the Client Satisfaction Questionnaire (CSQ-8), which ranges from 8-32 (higher scores indicate higher satisfaction) will determine acceptability	9-week active treatment phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol craving	The primary measure of alcohol craving will be the following single-item: How strong is your craving to drink alcohol? Scores range from 0 (none) to 20 (extremely strong).	9-week active treatment phase

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Rhode Island Hospital
• Investigators: Principal Investigator: Robert Miranda, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Alcohol; Clinical Trial; Medication; Teenager
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine
• Other Study ID Numbers: 2004002676; R21AA028394 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per sponsor requirements, all data will be uploaded to the NIAAA Data Repository.
• IPD Sharing Time Frame: One year after the completion of the project.
• IPD Sharing Access Criteria: As required by the Sponsor, the data from this clinical trial will be uploaded to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) data repository. Like all NIAAA grants, the NIAAA will govern the access criteria.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• 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.: No