Study of the Medication Prazosin for Alcohol Dependence

• Sponsor: Seattle Institute for Biomedical and Clinical Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00762710
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH), VA Puget Sound Health Care System (U.S. Fed), University of Washington (Other)
• Enrollment: 92
• Location: 1
• Arms: 2
• Actual Duration (Months): 77
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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

• Study Type: Interventional
• Actual Enrollment: 92 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
• Actual Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 - Prazosin Medication 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.	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 Names: Minipress
Placebo Comparator: 2 - Placebo Medication 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.	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; Other Names: No other intervention names

Outcome Measures

Primary Outcome Measures

1. Alcohol Consumption [12 weeks]

   At the baseline and final medication visits, the Form 90 (19) was used to assess alcohol and drug use for the preceding 90-day period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	VA Puget Sound Health Care System	Seattle	Washington	United States	98108

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

Study Documents (Full-Text)

• Informed Consent Form - Sep 9, 2013

More Information

Publications

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

• Responsible Party: Seattle Institute for Biomedical and Clinical Research
• ClinicalTrials.gov Identifier: NCT00762710
• Other Study ID Numbers: 1R01AA017184-01; 5R01AA017184-05
• First Posted: Sep 30, 2008
• Last Update Posted: Jun 4, 2020
• Last Verified: Jun 1, 2020

• 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; Prazosin

Study Results

Participant Flow

Recruitment Details	Recruitment began in January 2008 and ended June 2014. Six hundred and one people responding to flyers and newspaper advertisements and contacted the study, 151 provided informed consent, and 19 women and 73 men (N = 92) were randomized. Both civilian and veteran participants were seen in an outpatient VA clinic.
Pre-assignment Detail	Of the 151 consented into the study, 59 did not go onto be randomized because of the following: Declined after screen (N=11) (includes missing baseline/first medication appointment) Ineligible at screen (N=48) PTSD (N=11) Acute illness (N=7) Drug dependence (N=4) Drinking inclusion not met (N=20) Other (N=6)

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	Prazosin medication 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	Placebo medication 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
Period Title: Overall Study
STARTED	48	44
COMPLETED	27	29
NOT COMPLETED	21	15

Baseline Characteristics

Arm/Group Title	Prazosin	Placebo	Total
Arm/Group Description	Prazosin medication 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	Placebo medication 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	Total of all reporting groups
Overall Participants	48	44	92
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	48 100%	44 100%	92 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (9.8)	49.1 (9.5)	48.1 (9.7)
Sex: Female, Male (Count of Participants)
Female	11 22.9%	8 18.2%	19 20.7%
Male	37 77.1%	36 81.8%	73 79.3%
Region of Enrollment (Count of Participants)
United States	48 100%	44 100%	92 100%

Outcome Measures

1. Primary Outcome

Title	Alcohol Consumption
Description	At the baseline and final medication visits, the Form 90 (19) was used to assess alcohol and drug use for the preceding 90-day period
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Providing baseline and last week of medication information for all participants that completed the titration period (40 in each group).

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	Prazosin medication 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	Placebo medication 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
Measure Participants	40	40
Baseline % Days Heavy Drinking	71.8 (29.1)	66.5 (26.0)
Final medication week % Days Heavy Drinking	11.4 (22.8)	22.6 (34.1)

Adverse Events

Time Frame	Participants were monitored for adverse events after they started taking medications and about one month after they discontinued the medications. Because a few participants withdrew from the study after the baseline, where medications were dispensed, adverse events were monitored from one week to 16 weeks, depending on the length of participants' participation in the study.
Adverse Event Reporting Description	Participants were queried at every study visit with regard to potential adverse events and underwent clinical safety checks (e.g., sitting and stand blood pressures) at each visit.
Arm/Group Title	Prazosin		Placebo
Arm/Group Description	Prazosin medication 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		Placebo medication 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
All Cause Mortality
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		1/44 (2.3%)
Serious Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/48 (6.3%)		2/44 (4.5%)
Gastrointestinal disorders
medical hospitalization	0/48 (0%)	0	1/44 (2.3%)	1
Infections and infestations
Medical hospitalization	1/48 (2.1%)	1	0/44 (0%)	0
Psychiatric disorders
Death	0/48 (0%)	0	1/44 (2.3%)	1
inpatient alcohol detoxification	2/48 (4.2%)	2	0/44 (0%)	0
Other (Not Including Serious) Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/48 (58.3%)		15/44 (34.1%)
General disorders
Drowsiness	28/48 (58.3%)		15/44 (34.1%)

Limitations/Caveats

Lack of knowledge of optimal dosing for prazosin and medication adherence (medication adherence was suboptimal).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.