Alcoholism
Conditions
Keywords
Alcoholism, Heavy Drinking, Alcohol Dependence
Brief summary
This investigation will assess the effectiveness of topiramate in reducing ethanol consumption by alcohol dependent subjects. It also will seek to establish whether topiramate can be safely used in this population including whether it might be subject to abuse by alcohol dependent individuals. A secondary goal of this study is to assess the effects of topiramate on verbal fluency during treatment for alcohol dependence.
Detailed description
Alcoholism is a disorder that produces extensive morbidity and mortality. Substantial progress has been made in the development of medications that can help to promote abstinence in alcohol dependent individuals. However, investigations of the most promising drugs, particularly naltrexone and acamprosate, suggest that these agents have at best moderate efficacy and there is a great need for additional medications for the treatment of alcoholism. The results of a recent study suggest that the administration of the anticonvulsant agent ,topiramate helps alcoholic individuals to maintain abstinence (Johnson et al., 2003). The objectives of this study is to determine whether topiramate will reduce the consumption of alcohol in subjects dependent on this substance, as has been previously reported.Other study objectives are to assess the abuse liability properties of topiramate in alcohol dependent subjects and to examine the effects of chronic topiramate administration on cognitive functioning. This will be a thirteen week long open label clinical trial of the effects of topiramate administration on ethanol consumption by alcohol dependent subjects. Subjects will be asked to provide informed consent and then will be screened on the same day to determine if they meet study eligibility criteria. Subjects will be asked to return to provide two urines over the following week. Baseline measures of mood, craving, withdrawal, cognitive functioning and physical health will be obtained. In the afternoon they will receive their first dose of medication. Their responses to this medication challenge will be assessed over a 3-hour period. During the drug treatment phase subjects will be asked to come to the clinic weekly for assessment and manual guided therapy during weeks 1-4 and biweekly during weeks 6-8. On day 85 subjects will be seen at the clinic for a termination visit.
Interventions
DRUGTopiramate (Topamax)
Medication Dosing Schedule: Days 1-3 50 mg q PM Days 4-7 50 mg BID Days 8-11 50 mg q AM & 100 mg q PM Days 12-15 100mg BID Days 16-19 100 mg q AM & 150 mg q PM Days 20-23 150 mg BID Days 24-27 150 mg qAM & 200 mg q PM Days 28-70 200 mg BID Days 71-77 150 mg BID Days 78-84 100mg BID Days 85-87 50 mg BID Days 88-91 50 mg qPM
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Boston University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. DSM-IV Diagnosis of Alcohol Dependence; Minimal drinking level of 14 drinks per week for women and 20 drinks per week for men over a consecutive 30 day period during the last 90 days 2. Intent to stop drinking 3. Male or female age 18-65 4. Able to maintain sobriety for 3 consecutive days without the use of detoxification medications 5. Able to provide informed consent and to comprehend study procedures. 6. If a woman, then is willing to use an effective means of birth control during throughout the study period. These include: a. barrier (diaphragm or condom) with spermicide b.intrauterine progesterone contraceptive system c. levonorgestrel implant d. medroxyprogesterone acetate contraceptive injection e. complete abstinence
Exclusion criteria
1. Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine, or caffeine as assessed by urine toxicology (2 out of 3 Dependent on or extensive abuse of drugs or substances other than positive consecutive urines) 2. DSM IV Axis I diagnoses other than ethanol, caffeine, or nicotine dependence severe enough to require treatment with medication or to prevent compliance with the protocol. 3. Currently being treated with disulfiram (Antabuse), naltrexone (ReVia), or acamprosate 4. Currently being treated with any other psychoactive or other CNS medications or a carbonic anhydrase inhibitor (e.g. acetazolamide) 5. In need of medical detoxification from alcohol. 6. Prior history of kidney stones. 7. History of liver disease. ALT or AST 3 times higher than upper range of normal values. 8. BUN or serum creatinine outside the normal range 9. Major neurological disorder including seizures 10. Other major diseases including severe hypertension, renal disease, or cardiac disease. 11. Prior participation within 60 days in another clinical study. 12. If female, a positive serum HCG or breast feeding. 13. If female using oral contraceptives as a means of birth control. 14. History of allergic sensitivity to topiramate 15. Pending imprisonment 16. Cardiac pacemaker or metal surgical implant. 17. History of angle closure glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method | 70 days | The primary outcome was the mean daily consumption of standard alcoholic drinks (14 g per ethanol) during the baseline week compared to week 10, the final week subjects were one maintenance dose of topirmate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phonetic Portion of the Controlled Word Association Test (COWAT) | Baseline compared to Week 10 | Phonetic COWAT is a measure of verbal fluency. Results are in terms of number of words produced starting with a set of particular letters.This involves a comparison of baseline and Week 10 COWAT scores |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Treatment In this open label non-placebo controlled trial all subjects received topiramate, the active medication. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Topiramate Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age Continuous | 50.7 years STANDARD_DEVIATION 8.9 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method
The primary outcome was the mean daily consumption of standard alcoholic drinks (14 g per ethanol) during the baseline week compared to week 10, the final week subjects were one maintenance dose of topirmate.
Time frame: 70 days
Population: An ITT approach was used in the analysis. Least squares value for the baseline and 10 week of treatment were compared using a t test with Dunnett-Hsu adjustment. Differences between these means are presented as the result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate Treatment | The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method | -4.9 Standard Drink (14 g alcohol) | Standard Error 0.86 |
Comparison: This was a within subject analysis. The null hypothesis was that there would be no significant difference in least squares means values obtained for the baseline and week 10 assessment weeks.p-value: <0.000195% CI: [-6.58, -3.14]Mixed Models Analysis
Secondary
Phonetic Portion of the Controlled Word Association Test (COWAT)
Phonetic COWAT is a measure of verbal fluency. Results are in terms of number of words produced starting with a set of particular letters.This involves a comparison of baseline and Week 10 COWAT scores
Time frame: Baseline compared to Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate Treatment | Phonetic Portion of the Controlled Word Association Test (COWAT) | -11 Number of words | Standard Error 2.7 |
Comparison: This is a within subject comparison of COWAT scores botained for the baseline session and the Week 10 session. The null hypothesis is that there would be no difference between these scores.p-value: 0.001Mixed Models Analysis