Clinical trial NCT00762710: Study of the Medication Prazosin for Alcohol Dependence
Official title: Clinical Trial of the Adrenergic Alpha-1 Antagonist Prazosin for Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholism
Keywords: Alcohol
Abuse
Use
Disorder
Dependence
Symptoms
Alcoholic
Alcoholism
Prazosin
Drug
Medicine
Medication
Treatment
Study
Placebo
Medical
Management
Craving
Consumption
Binge
Drinking
Drink
Heavy
Lead sponsor: Seattle Institute for Biomedical and Clinical Research
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: VA Puget Sound Health Care System
name: University of Washington
First posted: 2008-09-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Alcohol Consumption
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System
name: Tracy L Simpson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/01.mlr.0000204052.95507.5c.
citation: 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. doi: 10.1177/1740774507076923.
citation: 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. doi: 10.1001/jama.295.17.2003.
citation: 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. doi: 10.15288/jsa.2005.66.121.
citation: McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA. 1993 Nov 10;270(18):2207-12.
citation: Simpson TL, Saxon AJ, Stappenbeck C, Malte CA, Lyons R, Tell D, Millard SP, Raskind M. Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder. Am J Psychiatry. 2018 Dec 1;175(12):1216-1224. doi: 10.1176/appi.ajp.2018.17080913. Epub 2018 Aug 29.