Alcohol Use Disorder
Conditions
Keywords
Alcohol, Teenager, Medication, Clinical Trial
Brief 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.
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.
Interventions
DRUGLamotrigine
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).
DRUGPlacebo
Matching placebo (sugar pill)
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Rhode Island Hospital
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
* 16 to 24 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion Rates | 9-week active treatment phase | The number and percentage of youth who complete the active medication phase will determine feasibility. |
| Acceptability of the Study Medication | 9-week active treatment phase | The Client Satisfaction Questionnaire (CSQ-8) ranges from 8 to 32 (higher scores indicate higher satisfaction) and will determine acceptability. Treatment satisfaction will be considered acceptable if the number and percentage of subjects who rate their treatment experience in the satisfactory or highly satisfactory ranges on the CSQ-8 is equal to or greater than 80%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | 9-week active treatment phase | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine Lamotrigine (25 mg/day to 200 mg/day in two divided doses) for 9 weeks
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). | 23 |
| Placebo Identical matching placebo capsules
Placebo: Matching placebo (sugar pill) | 21 |
| Total | 44 |
Baseline characteristics
| Characteristic | Lamotrigine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 19.61 years STANDARD_DEVIATION 1.34 | 20.33 years STANDARD_DEVIATION 1.43 | 19.95 years STANDARD_DEVIATION 1.41 |
| Alcohol drinks consumed per drinking day (Mean) | 4.35 Count of Standard Alcoholic Drinks STANDARD_DEVIATION 1.49 | 4.15 Count of Standard Alcoholic Drinks STANDARD_DEVIATION 1.55 | 4.25 Count of Standard Alcoholic Drinks STANDARD_DEVIATION 1.5 |
| Drinking Days (%) | 34.32 Percentage STANDARD_DEVIATION 11.78 | 37.07 Percentage STANDARD_DEVIATION 19.22 | 35.63 Percentage STANDARD_DEVIATION 9.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 19 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 14 Participants | 26 Participants |
| Region of Enrollment United States | 23 participants | 21 participants | 44 participants |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 21 |
| other Total, other adverse events | 21 / 23 | 20 / 21 |
| serious Total, serious adverse events | 0 / 23 | 0 / 21 |
Outcome results
Primary
Acceptability of the Study Medication
The Client Satisfaction Questionnaire (CSQ-8) ranges from 8 to 32 (higher scores indicate higher satisfaction) and will determine acceptability. Treatment satisfaction will be considered acceptable if the number and percentage of subjects who rate their treatment experience in the satisfactory or highly satisfactory ranges on the CSQ-8 is equal to or greater than 80%.
Time frame: 9-week active treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lamotrigine | Acceptability of the Study Medication | 20 Participants |
| Placebo | Acceptability of the Study Medication | 19 Participants |
Primary
Completion Rates
The number and percentage of youth who complete the active medication phase will determine feasibility.
Time frame: 9-week active treatment phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lamotrigine | Completion Rates | 22 Participants |
| Placebo | Completion Rates | 19 Participants |
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).
Time frame: 9-week active treatment phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Alcohol Craving | 3.14 units on a scale | Standard Deviation 3.41 |
| Placebo | Alcohol Craving | 3.81 units on a scale | Standard Deviation 4.57 |