Effects of Topiramate on Adolescent Alcohol Use: Efficacy and Mechanisms

Study Overview
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Brief Summary
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This study will help to determine whether the medication, topiramate, reduces alcohol use among adolescents with alcohol dependence. It will also help answer the question, How does topiramate reduce drinking in teenagers? Understanding how topiramate may reduce drinking in adolescents would allow for a more targeted pharmacotherapeutic approach to treatment and help to identify additional medications that may hold promise for improving treatment outcomes for youth.

Detailed Description
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Adolescent alcohol use is associated with myriad adverse legal, health, and educational consequences and contributes to the leading causes of mortality among youth. Yet despite the magnitude of this public health problem, treatment initiatives for youth remain inadequate. Given these data, the National Institute on Alcohol Abuse and Alcoholism identified the critical need for medications development research for youth with the goal of identifying promising agents for which large-scale clinical trials are justified. The long-term goal of this research program is to improve pharmacotherapy for alcoholism. The major objective of this project is to address the urgent need for empirical data on medications that may benefit youth. For the past 10 years our research program has successfully paired human laboratory paradigms with ecological momentary assessment (EMA), whereby research participants use handheld electronic diaries to monitor their drinking, craving, and sensitivity to alcohol in real time in their natural environment. Using this approach, we identified mechanisms by which medications act and patient characteristics that moderate these effects. The proposed study will test if and how topiramate (TPM), an anticonvulsant shown to be efficacious for treating adults, reduces drinking in youth. To this end, we will randomize adolescent problem drinkers to TPM or placebo for 8 weeks, in combination with biweekly motivational enhancement therapy sessions, using a two-group, double-blind design. While at the target dose (200 mg/day) youth will complete EMA in their natural environment. In addition, youth will complete alcohol cue reactivity assessments in the laboratory to test the effects of TPM on cue-elicited craving and physiological reactivity in a controlled environment. Youth will complete 6- and 12-month follow-up assessments to determine whether any benefits are sustained. This study will provide much needed data on the tolerability and efficacy of TPM with adolescents, while adding important new information about the biobehavioral mechanisms of TPM action in youth.

Official Title
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Effects of Topiramate on Adolescent Alcohol Use: Efficacy and Mechanisms

Conditions
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Alcohol Drinking

Intervention / Treatment
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* Drug: Topiramate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 14-24 years old (inclusive) Non-treatment seeking for alcohol abuse or dependence Interest in reducing alcohol use Self-reported alcohol use at least 2 days/week during prior 28 days Able to read simple English Exclusion Criteria: Alcohol or substance abuse treatment in the past 30 days Clinically significant medical abnormalities History of renal impairment, renal stones, or unstable hypertension History of progressive neurodegenerative disorders or clinical significant neurological disorders Body mass index lower than 18 Pregnant, nursing, or refusal to use reliable birth control, if female Non-stabilized psychotropic medication and/or taking medication that is contraindicated for use with topiramate Medications that may effect alcohol use or a carbonic anhydrase inhibitor Suicidal or psychotic Current coexisting substance use disorders other than alcohol, caffeine, cannabis, or nicotine use disorders Clinically significant alcohol withdrawal symptoms Impaired cognitive functioning Living with an active study participant Compelled to treatment by the juvenile justice system

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topiramate<br>Topiramate (200 mg) taken orally daily | Drug: Topiramate<br>* Topiramate (200 mg daily)<br>* Other names: Topamax;|
| Placebo Comparator: Sugar pill<br>Placebo (sugar pill) taken orally daily | Drug: Placebo<br>* Matching placebo capusules (sugar pills<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Use | Percent drinking days at the target medication dose | Study Weeks 5-8 | 
| Heavy Drinking Days | Percent heavy drinking days at the target medication dose. Heavy drinking is defined as 4 or more standard alcoholic drinks per day for females and 5 or more standard drinks per day for males. | Study Weeks 5-8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Use | Percent drinking days at the 6-month follow-up assessment | 6-month follow-up assessment | 
| Alcohol Use | Percent drinking days at the 12-month follow-up assessment | 12-month follow-up assessment |