Alcohol Drinking
Conditions
Brief summary
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
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.
Interventions
DRUGTopiramate
Topiramate (200 mg daily)
DRUGPlacebo
Matching placebo capusules (sugar pills
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
14 Years to 24 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Use | Study Weeks 5-8 | Percent drinking days at the target medication dose |
| Heavy Drinking Days | Study Weeks 5-8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Use | 6-month follow-up assessment | Percent drinking days at the 6-month follow-up assessment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Topiramate (200 mg) taken orally daily | 41 |
| Sugar Pill Placebo (sugar pill) taken orally daily | 41 |
| Total | 82 |
Baseline characteristics
| Characteristic | Topiramate | Sugar Pill | Total |
|---|---|---|---|
| Age, Continuous | 20.88 Years STANDARD_DEVIATION 2.08 | 20.49 Years STANDARD_DEVIATION 2.05 | 20.68 Years STANDARD_DEVIATION 2.06 |
| Region of Enrollment United States | 41 Participants | 41 Participants | 82 Participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 41 |
| other Total, other adverse events | 37 / 41 | 35 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 |
Outcome results
Primary
Alcohol Use
Percent drinking days at the target medication dose
Time frame: Study Weeks 5-8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Alcohol Use | 29.59 Percent of days | Standard Deviation 19.55 |
| Sugar Pill | Alcohol Use | 27.08 Percent of days | Standard Deviation 21.47 |
Primary
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.
Time frame: Study Weeks 5-8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Heavy Drinking Days | 9.34 percentage of days | Standard Deviation 10.99 |
| Sugar Pill | Heavy Drinking Days | 6.78 percentage of days | Standard Deviation 11.44 |
Secondary
Alcohol Use
Percent drinking days at the 6-month follow-up assessment
Time frame: 6-month follow-up assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Alcohol Use | 23.56 Percent of days | Standard Deviation 17.11 |
| Sugar Pill | Alcohol Use | 21.75 Percent of days | Standard Deviation 21.5 |
Secondary
Alcohol Use
Percent drinking days at the 12-month follow-up assessment
Time frame: 12-month follow-up assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Alcohol Use | 25.55 Percent of days | Standard Deviation 22.03 |
| Sugar Pill | Alcohol Use | 21.93 Percent of days | Standard Deviation 21.73 |