Alcohol Abuse, Drug Abuse
Conditions
Keywords
keppra, levetiracetam, alcoholism, genetics, subjective report
Brief summary
The overall goals of this study are to (1) expand knowledge about interactions of levetiracetam with alcohol by assessing the effects of levetiracetam compared to placebo in moderate and heavy social alcohol users and (2) to test the AccuswayTM platform as a tool to measure postural control (which has been used as a marker of intoxication) and the effects of levetiracetam on postural control.
Detailed description
The investigators propose a 42-day, double-blind, placebo-controlled crossover study in light to moderate and heavy alcohol users who are social drinkers. The specific aims are to: 1. Determine if levetiracetam alters daily alcohol consumption by comparing the mean drinks consumed per day during levetiracetam administration compared with the mean drinks per day consumed during placebo administration. 2. Obtain blood that will be banked for future genetic analysis of polymorphisms in genes that may predict the level of response to alcohol or effects of levetiracetam on alcohol consumption. 3. Test whether the AccuswayTM platform can detect changes in body sway in light to moderate or heavy social drinkers and in subjects taking levetiracetam versus placebo.
Interventions
Group A: Twenty moderate to heavy social alcohol users will receive 250 mg of levetiracetam BID (500 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 500 mg of levetiracetam BID (1,000 mg/day) x 7 days. Group B: Twenty moderate to heavy social alcohol users will receive 500 mg levetiracetam BID (1000 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 1000 mg levetiracetam BID (2,000 mg per day) x 7 days.
DRUGPlacebo
Sponsors
United States Department of Defense
University of California
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adults who are social drinkers 21 and 50 years of age. 2. Moderate to heavy social drinkers (women=7-21 drinks/week, men=7-25 drinks/week). 3. Body Mass Index (BMI)\>18 and \<30. 4. If female, must be non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device \[IUD\], hormonal birth control, or double barrier method \[male condom, female condom, or diaphragm plus a spermicidal agent such as contraceptive foam, jelly or cream\]). 5. Able and willing to provide written informed consent. 6. Able to understand and follow the instructions of the investigator, and understand all rating scales. 7. Have a negative urine drug screen at all visits, with the exception of cannabinoids.
Exclusion criteria
1. Positive urine drug screen, except cannabinoids. Occasional cannabinoid use is allowed, however daily use, dependence, or if considered more than a casual user by study physician, subject will be excluded. 2. Use of cocaine, amphetamines or other stimulants, hallucinogens, ecstasy or other psychoactive drugs, greater than 10 times in the last 24 months or at anytime in the past 60 days. 3. Lifetime use of PCP or ketamine greater than 10 times, or at any time in the last 24 months. 4. History of abusing inhalants (such as glue, toluene or other volatile substances). 5. Current or past dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol, as determined by the study physician's assessment. 6. Current or prior enrollment in an alcohol or other drug treatment program, or current legal problems relating to alcohol or other drug use, including awaiting trial or supervision by a parole or probation officer. 7. Binge drinking more than three times per week (binge defined as \>5 standard drinks in one session). 8. Alcohol consumption \>21 drinks/week for women and \>25 drinks/week for men. 9. Currently trying to quit alcohol and/or recreational drug use. 10. Positive for lifetime abnormal opioid use or prescription drug abuse. 11. Clinically significant medical or psychiatric illness (including anxiety or panic disorders) as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician. 12. Bilirubin more than 2 times the normal upper limit. 13. AST (SGOT), ALT (SGPT), or alkaline phosphatase more than 2 times the normal upper limit. 14. Body Mass Index \>30 or \<18 15. Pregnancy or a woman of child bearing potential not currently using an adequate means of contraception. 16. Currently taking any medication other than over-the-counter nonsteroidal anti-inflammatories, acetaminophen, inhaled asthma therapy, contraceptives, nicotine patches, and over-the-counter non-sedating antihistamines.NSAIDs, acetaminophen, or any other OTC (including herbal) medication (unless cleared by study physician). 17. BAC level greater than 0.02% at the beginning of visits 1, 7, or 8 (within margin of error for detection). 18. Estimated creatinine clearance \< 50 ml/min. 19. Chronic pain condition requiring regular physician visits and treatment under a physician's supervision. 20. Neurological dysfunction or psychiatric disorder severe enough to interfere with assessment of outcome measures as defined above. 21. Allergy to levetiracetam. 22. Significant cardiac pathology or abnormal initial EKG with QT/QTc interval prolongation \> 480 m secs at baseline. 23. Has received an investigational drug within 30 days prior to Study Visit 2 (after screening visit). 24. Subjects who are unable to read or speak English. 25. Those, in the opinion of the investigator, who are considered unable to adhere to scheduled appointments, unlikely to comply with the study protocol, or who are unsuitable for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standard Alcoholic Drinks Per Treatment Period | During each 14 day treatment period | The primary outcome of this study is to determine the effect of levetiracetam on alcohol consumption as measured by change in # of drinks during each treatment period. |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted online (Craigslist) and from publicly posted flyers.
Pre-assignment details
Enrolled participants were excluded prior to medication dosing if blood testing revealed elevated liver enzymes or if urine testing indicated a pregnancy.
Participants by arm
| Arm | Count |
|---|---|
| Group A: Crossover Between Low Dose Keppra and Placebo Group A: Twenty moderate to heavy social alcohol users (women 7-20 drinks/week --moderate 7-14 and heavy 15-20 and men 15-25 drinks/week --moderate 7-14 and heavy 15-25 drinks/week) will receive 250 mg of levetiracetam BID (500 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 500 mg of levetiracetam BID (1,000 mg/day) or will receive a double dose of placebo x 7 days. Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. | 23 |
| Group B: Crossover Between High Dose Keppra and Placebo Group B: Twenty moderate to heavy social alcohol users (women 7-20 drinks/week --moderate 7-14 and heavy 15-20 and men 15-25 drinks/week --moderate 7-14 and heavy 15-25 drinks/week) will receive 500 mg levetiracetam BID (1000 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 1000 mg levetiracetam BID (2,000 mg per day) x 7 days or will receive a double dose of placebo x 7 days.
Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Group A: Crossover Between Low Dose Keppra and Placebo | Group B: Crossover Between High Dose Keppra and Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Region of Enrollment United States | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 46 | 0 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 |
Outcome results
Primary
Standard Alcoholic Drinks Per Treatment Period
The primary outcome of this study is to determine the effect of levetiracetam on alcohol consumption as measured by change in # of drinks during each treatment period.
Time frame: During each 14 day treatment period
Population: All study participants were used for data analysis. If there were no significant differences between the two doses of levetiracetam, data would be collapsed for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Subjects (n = 46) Placebo | Standard Alcoholic Drinks Per Treatment Period | 41.2 number of drinks per treatment period | Standard Error 2.8 |
| All Subjects (n = 46) Levetiracetam | Standard Alcoholic Drinks Per Treatment Period | 45.4 number of drinks per treatment period | Standard Error 3.6 |