Medication Development in Alcoholism: Acamprosate Versus Naltrexone

Study Overview
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Brief Summary
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The purpose of this study is to develop and validate a human laboratory model for prediction of medication efficacy in clinical trials for relapse prevention in alcohol dependence.

Detailed Description
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This is a double-blind, 3-cell, outpatient human laboratory study to determine the degree to which acamprosate and naltrexone will suppress subjective and physiological responsivity to alcohol cues relative to placebo in early abstinence.

Official Title
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Medication Development in Protracted Abstinence in Alcoholism: Acamprosate Versus Naltrexone

Conditions
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Alcoholism

Intervention / Treatment
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* Drug: Acamprosate
* Drug: Naltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥ 18 and ≤ 55 years of age Meets Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) criteria for current alcohol dependence Does not desire treatment Alcohol free, as verified by breath alcohol concentration, with a Clinical Institute Withdrawal Assessment (CIWA) ≤ 8, at the time of testing, with no evidence of drinking for at least 3 days but no more than 7 days prior to the cue reactivity session Able to complete and understand questionnaires and study procedures in English Verbal I.Q. estimate ≥ 85 Signed informed consent Exclusion Criteria: Currently meets DSM-IV criteria for dependence on substances other than alcohol or nicotine Significant medical disorders that will increase potential risk or interfere with study participation Sexually active women with childbearing potential who are pregnant, nursing, or refuse to use a reliable method of birth control Meets DSM-IV criteria for a major Axis I disorder, including depression or anxiety disorders Treatment within the month prior to screening with investigational medications or those which may influence drinking outcome, e.g., disulfiram (Antabuse), naltrexone (ReVia), acamprosate (Campral), antidepressants or other psychotropic agents Chronic treatment with any narcotic-containing medications during the previous month or evidence of current opiate use Liver function tests more than three times normal or elevated bilirubin No fixed domicile and/or no availability by telephone or beeper Current involvement in or plans for treatment prior to study completion Patients who have a history of adverse drug reactions to the study drugs or their ingredients Failure to take double-blind medication as prescribed Inability to understand or comply with the provisions of the protocol or consent form

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Acamprosate | Drug: Acamprosate<br>* Two 333mg capsules, 3 times daily (Total dose, 1998 mg daily), 1 week duration<br>* Other names: Campral;|
| Active Comparator: 2<br>Naltrexone | Drug: Naltrexone<br>* 50mg capsule, Once daily, 1 week duration<br>* Other names: ReVia;|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Matched placebo capsule, 1 week duration<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | The four Visual Analog Scale questions assess domains of alcohol craving: the intention to drink, loss of control, relief craving, and urge intensity. The scale ranges from 0-20 where a zero indicates no craving and 20 indicates severe craving; thus, a higher score indicates a worse outcome. Total is a summation of the four subscales (i.e. Strength, Intent, Impulse, Relief) and ranges in value from 0-80 with higher scores indicative of a worse outcome. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Standard Drinks Per Week at 1 Week | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 1 - Baseline). More negative values indicate less use of alcohol. | 1 week | 
| Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | The BDI-II is a self-rating of severity of depressive symptoms. BDI-II Total scores range from 0-63; a lower score indicates less severe depressive systems and thus is a better outcome. Change = (Week 1 score - Baseline score). The Total score is a sum of the 21 items on the BDI-II instrument, with each item rated from 0-3. | 1 week | 
| Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | The PSQI is an instrument to assess subjective sleep quality and disturbance. The Total score ranges from 0 to 21 where a lower score is better sleep quality. Change = (Week 1 score - Baseline score). Seven subscales (range 0-3) are summed to compute the Total score. | 1 week | 
| Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | The ACQ-SF is an assessment of current drinking urges, difficulty resisting urge and anticipation of positive outcome or relief from negative state by drinking. The Total score ranges from 0 to 7 where a lower score is a better outcome. Change = (Week 1 score - Screening score). The scale is comprised of twelve items (range 0-7) that are averaged to compute the Total score. | 2 weeks |