Enhancing the Effects of Alcohol Treatment With Lamotrigine

Alcohol Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04770493
• Other study ID #: 2004002676
• Secondary ID: R21AA028394
• Status: Recruiting
• Phase: Phase 2
• Start date: January 24, 2022
• Est. completion date: October 2024

Study information

• Verified date: March 2023
• Source: Brown University
• Contact: Robert Miranda, PhD
• Phone: (401) 863-6658
• Email: Robert_Miranda_Jr[@]brown.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 19 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

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).
• Placebo
Matching placebo (sugar pill)

Locations

Country	Name	City	State
United States	Brown University Center for Alcohol and Addiction Studies	Providence	Rhode Island

Sponsors (3)

Lead Sponsor	Collaborator
Brown University	National Institute on Alcohol Abuse and Alcoholism (NIAAA), Rhode Island Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Completion rates	Percentage of youth who complete the active medication phase will determine feasibility.	9-week active treatment phase
Primary	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	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