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Prazosin and Naltrexone (PaN) Study for Veterans With Alcohol Use Disorders

NCT ID: NCT02322047

Last Updated: 2020-12-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-03

Study Completion Date

2018-10-10

Brief Summary

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The purpose of this study is to evaluate whether the combination of prazosin and naltrexone will decrease alcohol cravings and drinking in individuals who have problems with alcohol and have used alcohol at risky levels compare to naltrexone and placebo (Nal/Pl), prazosin and placebo (Praz/Pl), and double-placebo (Pl/Pl). We hypothesize that those assigned to both prazosin and naltrexone would report significantly greater decreases in percent drinking days and heavy drinking days as well as significantly greater reduction in craving from pre to post-treatment than those assigned to either single medication or double-placebo.

Prazosin is a medication that is approved by the U.S. Food and Drug Administration (FDA) to treat people with high blood pressure. Some studies have shown that prazosin may also decrease nightmares and improve sleep in Veterans suffering from Posttraumatic Stress Disorder (PTSD). Animal studies have consistently found that prazosin is associated with decreased alcohol consumption and that the combination of prazosin and naltrexone outperforms either medication alone. The current study is evaluating an "off-label" use of prazosin to determine whether it is helpful in decreasing alcohol cravings and consumption among people with alcohol problems. "Off-label" means that the FDA has not approved the use of prazosin for alcohol problems.

Naltrexone is a medication that is FDA approved for treating alcohol problems.

This study is sponsored by the Department of Defense and the Congressionally Directed Medical Research Program (DoD/CDMRP). We expect approximately 120 participants in this study, which will run over approximately 4 years. Study participants will be involved in the study for 7 weeks, or until they complete the Final Assessment.

Detailed Description

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In this double-blind, double-dummy, placebo-controlled study of prazosin and naltrexone, we will evaluate the combination of naltrexone and the noradrenergic medication prazosin (Nal/Praz) relative to naltrexone and placebo (Nal/Pl), prazosin and placebo (Praz/Pl), and double-placebo (Pl/Pl). Participants will undergo two craving inductions, one oriented towards relief craving and the other towards reward craving. Daily IVR (Interactive Voice Recording System) data on craving and consumption and PTSD symptomatology will be collected during the 7 days immediately following the initial assessment visit to establish a pre-medication baseline. One hundred twenty individuals with adequate IVR compliance and whose screening lab tests indicate it is safe for them to take the study medications will enter the medication phase of the study within 14 days of the initial assessment initiating prazosin/placebo as well as 50mg naltrexone/placebo treatment. Randomization will be blocked by gender, PTSD status, and desire to abstain vs. desire to cut down. Prazosin will be titrated to three times daily dosing (9 am: 4mg; 3pm: 4 mg; 9pm: 8mg) at the end of two weeks. Naltrexone will be taken once daily 50 mg/day with no titration schedule. The stable dose of both medications will continue for four more weeks and medication compliance will be evaluated through pill counts, the IVR daily monitoring, and riboflavin trace in urine analysis. On approximately day 42 participants will come into the lab for the craving inductions (there will be a two week window after day 42 in which participants may still be seen if scheduling issues arise). The order of the craving inductions will be counterbalanced, and their administration will be separated in time by 30 minutes to minimize carry over between them. Subjective responses to the craving inductions will be obtained via relief oriented craving items and reward oriented craving items from the Desire for Alcohol Questionnaire. Participants will then be assisted in returning their craving levels to baseline prior to debriefing. They will all be offered treatment referrals within the Veterans Affairs (VA) or in the community. Both prazosin and naltrexone can be safely discontinued without tapering.

Conditions

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Alcohol Use Disorder Posttraumatic Stress Disorder (PTSD)

Keywords

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Alcohol Drinking Craving Drinking Behavior Prazosin Naltrexone Adrenergic Alpha-1 Receptor Antagonists Adrenergic Antagonists Adrenergic Alpha-Antagonists mu-Opioid Receptor Antagonist Opioid Antagonist Alcohol Use Disorder Posttraumatic Stress Disorder PTSD Alcohol Treatment Alcohol Dependence Pharmacology Treatment AUD Alcohol Abuse Substance Use Disorder SUD Substance Abuse Addiction Alcohol Addiction Substance Addiction Substance Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eligible participants will be randomized into one of four study conditions: Naltrexone/Prazosin (Nal/Praz), Naltrexone/Placebo (Nal/Pl), Prazosin/Placebo (Praz/Pl), and Placebo/Placebo (Pl/Pl). Randomization will be blocked by gender, PTSD status, and alcohol consumption goal (abstention vs. reduction) and will be conducted by a VA Puget Sound Research Pharmacist using randomization tables supplied by the study Principal Investigator (PI). The Research Pharmacist will have no additional contacts with the participants.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
No study staff, including the participants, will know which condition the participants are in. Only the Research Pharmacist will know the participants' conditions.

Study Groups

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Praz/Nal

Prazosin and Naltrexone.

Prazosin will be taken following this titration schedule:

Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Naltrexone will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.

Group Type EXPERIMENTAL

Prazosin

Intervention Type DRUG

Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Naltrexone

Intervention Type DRUG

Naltrexone Dosing Days 1-42: 50mg @ 9PM

Praz/Pl

Prazosin and Placebo (Naltrexone)

Prazosin will be taken following this titration schedule:

Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Naltrexone Placebo will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.

Group Type ACTIVE_COMPARATOR

Prazosin

Intervention Type DRUG

Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Placebo (Naltrexone)

Intervention Type DRUG

Placebo Dosing Days 1-42: 50mg @ 9PM

Nal/Pl

Naltrexone and Placebo (Prazosin)

Prazosin Placebo will be taken following this titration schedule:

Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Naltrexone will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.

Group Type ACTIVE_COMPARATOR

Naltrexone

Intervention Type DRUG

Naltrexone Dosing Days 1-42: 50mg @ 9PM

Placebo (Prazosin)

Intervention Type DRUG

Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Pl/Pl

Placebo (Prazosin) and Placebo (Naltrexone)

Prazosin Placebo will be taken following this titration schedule:

Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Naltrexone Placebo will be taken from day 1 to day 42 at 9 PM. Dose: 50 mg.

Group Type PLACEBO_COMPARATOR

Placebo (Prazosin)

Intervention Type DRUG

Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Placebo (Naltrexone)

Intervention Type DRUG

Placebo Dosing Days 1-42: 50mg @ 9PM

Interventions

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Prazosin

Prazosin Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Intervention Type DRUG

Naltrexone

Naltrexone Dosing Days 1-42: 50mg @ 9PM

Intervention Type DRUG

Placebo (Prazosin)

Placebo Dosing Days 1-2: 1 mg @ 9PM Days 3-4: 1 mg @ 9AM, 3PM, 9PM Days 5-7: 2 mg @ 9AM, 3PM, 9PM Days 8-10: 2mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 11-14: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM Days 15-42: 4mg @ 9 AM, 3 PM; 8mg @ 9 PM

Intervention Type DRUG

Placebo (Naltrexone)

Placebo Dosing Days 1-42: 50mg @ 9PM

Intervention Type DRUG

Other Intervention Names

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Minipress Placebo Placebo

Eligibility Criteria

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Inclusion Criteria

1. Veteran of the U.S. military or National Guard Reserve.
2. Current AUD by DSM-5 criteria.
3. Heavy drinking (\>14 drinks per week for females; \> 21 drinks per week for males) for at least 2 weeks in the last 3 months and some drinking during the past two weeks OR binge drinking for at least 3 days in the last month (4+ drinks for females; 5+ drinks for males).
4. At least mild alcohol craving as assessed by the Pennsylvania Alcohol Craving Scale (PACS; score \> 10) at baseline.
5. Age 18-80.
6. English fluency and literacy.
7. Trying or planning to try to cut down on or abstain from alcohol.
8. Good general medical health.
9. Capable of giving informed consent.

Exclusion Criteria

1. Uncontrolled psychiatric disorder with psychotic symptoms or cognitive impairment.
2. If taking psychiatric medication, NOT on a stable dose for at least 30 days prior to randomization.
3. Any suicidal ideation in the past 7 days, plan or intent past 6 months, or any suicide attempt past year.
4. Homicidal ideation with plan and intent in the past 30 days.
5. Patient Health Questionnaire-9 (PHQ-9) endorsement of hopelessness or self-harm/SI and/or sum scale score ≥ 19.
6. Any use of prazosin or naltrexone past 30 days.
7. Currently taking disulfiram or acamprosate OR planning to take any of these medications (including prazosin or naltrexone) during the study.
8. Current moderate or severe substance use disorder (past 30 days) on any psychoactive substance other than alcohol, nicotine, or cannabis, OR use of any amphetamine or opioid-containing medications during the previous 30 days.
9. Significant acute or chronic medical illness
10. Preexisting hypotension (sys \<100) or orthostatic hypotension (systolic drop of \> 20 mmHg; after two minutes of standing, or any drop with dizziness).
11. Allergy or previous adverse reaction to naltrexone, prazosin, quinazolines, or other α-1 adrenergic blockers or use of other α -1 adrenergic blocker.
12. Women who are pregnant, breastfeeding, or of childbearing potential and not using a contraceptive method judged by the investigator to be effective.
13. Legal involvement that could interfere with study participation, including being court ordered for treatment.
14. Signs or symptoms of withdrawal at time of initial consent.
15. Any participation in an experimental drug study or any addiction study past 30 days.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

VA Puget Sound Health Care System

FED

Sponsor Role collaborator

Seattle Institute for Biomedical and Clinical Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tracy Simpson, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System

Locations

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VA Puget Sound Healthcare System

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Berk E, Black J, Locastro J, Wickis J, Simpson T, Penk W. Traumatogenicity: effects of self-reported noncombat trauma on MMPIs of male Vietnam combat and noncombat veterans treated for substance abuse. J Clin Psychol. 1989 Sep;45(5):704-8. doi: 10.1002/1097-4679(198909)45:53.0.co;2-6.

Reference Type BACKGROUND
PMID: 2808725 (View on PubMed)

Simpson TL, Westerberg VS, Little LM, Trujillo M. Screening for childhood physical and sexual abuse among outpatient substance abusers. J Subst Abuse Treat. 1994 Jul-Aug;11(4):347-58. doi: 10.1016/0740-5472(94)90045-0.

Reference Type BACKGROUND
PMID: 7966505 (View on PubMed)

McCann BS, Simpson TL, Ries R, Roy-Byrne P. Reliability and validity of screening instruments for drug and alcohol abuse in adults seeking evaluation for attention-deficit/hyperactivity disorder. Am J Addict. 2000 Winter;9(1):1-9. doi: 10.1080/10550490050172173.

Reference Type BACKGROUND
PMID: 10914288 (View on PubMed)

Simpson TL. Women's treatment utilization and its relationship to childhood sexual abuse history and lifetime PTSD. Subst Abus. 2002 Mar;23(1):17-30. doi: 10.1080/08897070209511472.

Reference Type BACKGROUND
PMID: 12444358 (View on PubMed)

Simpson TL, Miller WR. Concomitance between childhood sexual and physical abuse and substance use problems. A review. Clin Psychol Rev. 2002 Feb;22(1):27-77. doi: 10.1016/s0272-7358(00)00088-x.

Reference Type BACKGROUND
PMID: 11793578 (View on PubMed)

Simpson TL. Childhood sexual abuse, PTSD, and the functional roles of alcohol use among women drinkers. Subst Use Misuse. 2003 Jan;38(2):249-70. doi: 10.1081/ja-120017248.

Reference Type BACKGROUND
PMID: 12625430 (View on PubMed)

Comtois KA, Tisdall WA, Holdcraft LC, Simpson T. Dual diagnosis: impact of family history. Am J Addict. 2005 May-Jun;14(3):291-9. doi: 10.1080/10550490590949479.

Reference Type BACKGROUND
PMID: 16019979 (View on PubMed)

Simpson TL, Kivlahan DR, Bush KR, McFall ME. Telephone self-monitoring among alcohol use disorder patients in early recovery: a randomized study of feasibility and measurement reactivity. Drug Alcohol Depend. 2005 Aug 1;79(2):241-50. doi: 10.1016/j.drugalcdep.2005.02.001. Epub 2005 Feb 25.

Reference Type BACKGROUND
PMID: 16002033 (View on PubMed)

Dobie DJ, Maynard C, Kivlahan DR, Johnson KM, Simpson T, David AC, Bradley K. Posttraumatic stress disorder screening status is associated with increased VA medical and surgical utilization in women. J Gen Intern Med. 2006 Mar;21 Suppl 3(Suppl 3):S58-64. doi: 10.1111/j.1525-1497.2006.00376.x.

Reference Type BACKGROUND
PMID: 16637948 (View on PubMed)

Bowen S, Witkiewitz K, Dillworth TM, Chawla N, Simpson TL, Ostafin BD, Larimer ME, Blume AW, Parks GA, Marlatt GA. Mindfulness meditation and substance use in an incarcerated population. Psychol Addict Behav. 2006 Sep;20(3):343-7. doi: 10.1037/0893-164X.20.3.343.

Reference Type BACKGROUND
PMID: 16938074 (View on PubMed)

Kaysen D, Simpson T, Dillworth T, Larimer ME, Gutner C, Resick PA. Alcohol problems and posttraumatic stress disorder in female crime victims. J Trauma Stress. 2006 Jun;19(3):399-403. doi: 10.1002/jts.20122.

Reference Type BACKGROUND
PMID: 16788998 (View on PubMed)

Simpson T, Jakupcak M, Luterek JA. Fear and avoidance of internal experiences among patients with substance use disorders and PTSD: the centrality of anxiety sensitivity. J Trauma Stress. 2006 Aug;19(4):481-91. doi: 10.1002/jts.20128.

Reference Type BACKGROUND
PMID: 16929503 (View on PubMed)

Simpson TL, Kaysen D, Bowen S, MacPherson LM, Chawla N, Blume A, Marlatt GA, Larimer M. PTSD symptoms, substance use, and vipassana meditation among incarcerated individuals. J Trauma Stress. 2007 Jun;20(3):239-49. doi: 10.1002/jts.20209.

Reference Type BACKGROUND
PMID: 17597132 (View on PubMed)

Kaysen D, Dillworth TM, Simpson T, Waldrop A, Larimer ME, Resick PA. Domestic violence and alcohol use: trauma-related symptoms and motives for drinking. Addict Behav. 2007 Jun;32(6):1272-83. doi: 10.1016/j.addbeh.2006.09.007. Epub 2006 Nov 13.

Reference Type BACKGROUND
PMID: 17098370 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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W81XWH-14-1-0025

Identifier Type: -

Identifier Source: org_study_id