Study of the Medication Prazosin for Alcohol Dependence

Seattle Institute for Biomedical and Clinical Research

Status and phase: Completed; Phase 2

Conditions: Alcoholism

Treatments: Drug: Prazosin medication; Drug: Placebo medication

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT00762710

5R01AA017184-05 (U.S. NIH Grant/Contract)

1R01AA017184-01

Details and patient eligibility

About

The purpose of this study is to determine whether the drug prazosin is effective for the treatment of alcohol dependency.

Full description

Alcohol dependence (AD) afflicts nearly 10% of the US population and causes marked medical morbidity and mortality, marked psychiatric morbidity, increased health care costs, and lost work hours (Saxon, Malte, Sloan, et al., 2006; McFall, Saxon, Thaneemit-Chen, et al., 2007). Alcohol dependence is a biologically, genetically based disease, yet the majority of clinically accepted treatments are behaviorally or psychosocially based (Anton, O'Malley, Ciraulo, et al., 2006; Todd, Armeli, Tennen, et al., 2005). Despite the initial success of these treatments, 40-70% of patients relapse within the first 12 months after treatment (McGinnis & Foege, 1993). Research is needed to develop more effective biological treatments.

Currently, only three pharmacological treatments are FDA approved for the treatment of alcohol dependence and all are sub-optimal. None of these medications directly target noradrenergic brain systems. Recent advances in understanding the neurobiology of substance dependence and relapse support the notion that adrenergic systems play a critical role in these processes.

In a 6-week, double-blind, placebo-controlled pilot study, we randomized 24 participants without PTSD entering treatment for AD to prazosin or identical appearing placebo (Simpson et al., 2009). The prazosin group reported no more adverse events than the placebo group, and controlling for drinks per week at baseline and week number, the prazosin group reported fewer drinks per week in the final 3 weeks of the study. These findings led us to conduct a larger trial to further evaluate prazosin for AD.

The current study is a 16-week, randomized, two group parallel-design, double-blind, placebo-controlled trial to evaluate the efficacy of prazosin for decreasing alcohol use and the subjective experience of alcohol craving in individuals without PTSD who are seeking treatment for AD. Following randomization, a 2-week titration period will be followed by 10 weeks of stable dosing of prazosin or placebo. Study participants will attend study visits at least weekly for 12 weeks and will complete a final follow-up one month after discontinuation of the medication phase of the study at 16 weeks post-randomization. All study participants will also participate in Medical Management (MM) treatment, a behavioral intervention that has demonstrated efficacy as a behavioral platform for treatment of AD (Anton, O'Malley, Ciraulo, et al., 2006). Study participants will not be involved in other professional counseling or substance abuse treatment during their study involvement, though 12-step meeting attendance is encouraged during MM. Daily monitoring of alcohol craving, alcohol use, other substance craving and substance use, medication compliance, and key psychiatric symptoms via toll-free telephone calls to an Interactive Voice Response (IVR) system will continue throughout the 16-week study. Outcome measures will address alcohol use and craving and include IVR reports of craving and use, the TLFB for alcohol use, Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (depression), urine toxicology analysis (UDA), and Breathalyzer readings.

Enrollment: 92 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Current primary DSM-IV diagnosis of alcohol dependence(AD)
• Heavy drinking in the last 30 days
• At least 18 years of age
• Good general medical health (see Exclusion Criteria below)
• Capacity to provide informed consent
• English fluency and literacy

Exclusion criteria

• Psychiatric/behavioral: current post-traumatic stress disorder(PTSD); psychiatric disorder requiring any medication other than anti-depressants; currently taking disulfiram, acamprosate, or naltrexone or planning to take any of these medications during the 12-week medication phase of the study; current dependence on any other psychoactive substance other than nicotine or cannabis; a current diagnosis of opioid abuse, use of any opioid- containing medications or benzodiazepines during the previous month, or UDA positive for opioids, benzodiazepines, or sedative hypnotics.
• Medical: significant acute or chronic medical illness; women who are pregnant, nursing infant(s), or of childbearing potential and not using a contraceptive method judged by the study physician or PA to be effective; signs or symptoms of alcohol withdrawal at the time of initial consent
• Legal involvement that could interfere with study treatment. Individuals court ordered for treatment will not be eligible to participate in this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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92 participants in 2 patient groups, including a placebo group

1 - Prazosin Medication

Experimental group

Description:

Following randomization, participants in this arm will receive a 2-week titration of Prazosin followed by 10 weeks of stable dosing of Prazosin. They will also attend study visits at least weekly for 12 weeks and will complete a final follow-up one month after discontinuation of the medication phase of the study at 16 weeks post-randomization.

Treatment:

Drug: Prazosin medication

2 - Placebo Medication

Placebo Comparator group

Description:

Following randomization, participants in this arm will receive a 2-week titration of placebo followed by 10 weeks of stable dosing of placebo. They will also attend study visits at least weekly for 12 weeks and will complete a final follow-up one month after discontinuation of the medication phase of the study at 16 weeks post-randomization.

Treatment:

Drug: Placebo medication