Study of the Medication Prazosin for Alcohol Dependence

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alcoholism	Drug: Prazosin medication; Drug: Placebo medication	Phase 2

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence
Study Start Date :	January 2009
Estimated Primary Completion Date :	November 2013
Estimated Study Completion Date :	November 2013

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 1; Prazosin medication	Drug: Prazosin medication; Form: Prazosin will be taken orally, in the form of pills. Dosing: 9 AM, 3 PM, 9 PM Days 1-2: 0 mg, 0 mg, 1 mg Days 3-4: 1 mg, 1 mg, 1 mg Days 5-7: 2 mg, 2 mg, 2 mg Day 8-10: 2 mg, 2 mg, 6 mg Day 11-14: 4 mg, 4 mg, 6 mg Day 15-84: 4 mg, 4 mg, 8 mg; Other Name: Minipress
Placebo Comparator: 2; Placebo medication	Drug: Placebo medication; Form: Placebo will be taken orally, in the form of pills. Dosing: 9 AM, 3 PM, 9 PM Days 1-2: 0 mg, 0 mg, 1 mg Days 3-4: 1 mg, 1 mg, 1 mg Days 5-7: 2 mg, 2 mg, 2 mg Day 8-10: 2 mg, 2 mg, 6 mg Day 11-14: 4 mg, 4 mg, 6 mg Day 15-84: 4 mg, 4 mg, 8 mg

Outcome Measures

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Primary Outcome Measures :

1. Alcohol consumption and cravings [ Time Frame: 16 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Ian Pocock, B.A.	206-277-4872
Contact: Bergetta Dietel, B.A.	206-277-4015

Locations

United States, Washington
VA Puget Sound Health Care System	Recruiting
Seattle, Washington, United States, 98108
Contact: Ian Pocock, B.A. 206-277-4872
Contact: Bergetta M Dietel, B.A 206-277-4015

Sponsors and Collaborators

Seattle Institute for Biomedical and Clinical Research

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

VA Puget Sound Health Care System

University of Washington

Investigators

Principal Investigator:	Tracy L Simpson, Ph.D.	VA Puget Sound Health Care System

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Saxon AJ, Malte CA, Sloan KL, Baer JS, Calsyn DA, Nichol P, Chapko MK, Kivlahan DR. Randomized trial of onsite versus referral primary medical care for veterans in addictions treatment. Med Care. 2006 Apr;44(4):334-42.

McFall M, Saxon AJ, Thaneemit-Chen S, Smith MW, Joseph AM, Carmody TP, Beckham JC, Malte CA, Vertrees JE, Boardman KD, Lavori PW. Integrating smoking cessation into mental health care for post-traumatic stress disorder. Clin Trials. 2007;4(2):178-89.

Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17.

Todd M, Armeli S, Tennen H, Carney MA, Ball SA, Kranzler HR, Affleck G. Drinking to cope: a comparison of questionnaire and electronic diary reports. J Stud Alcohol. 2005 Jan;66(1):121-9.

McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA. 1993 Nov 10;270(18):2207-12.

Responsible Party:	Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:	NCT00762710 History of Changes
Other Study ID Numbers:	1R01AA017184-01 ( U.S. NIH Grant/Contract )
First Posted:	September 30, 2008
Last Update Posted:	August 7, 2013
Last Verified:	August 2013

Keywords provided by Seattle Institute for Biomedical and Clinical Research:

Alcohol; Abuse; Use; Disorder; Dependence; Symptoms; Alcoholic; Alcoholism; Prazosin; Drug; Medicine; Medication	Treatment; Study; Placebo; Medical; Management; Craving; Consumption; Binge; Drinking; Drink; Heavy

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Ethanol; Prazosin; Anti-Infective Agents, Local; Anti-Infective Agents	Central Nervous System Depressants; Physiological Effects of Drugs; Antihypertensive Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action