Alcohol Use DisorderPhase 2PaNNCT02322047

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

A Phase 2 study testing Prazosin and Naltrexone in people with Alcohol Use Disorder and Posttraumatic Stress Disorder (PTSD), run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Alcohol Use Disorder, Posttraumatic Stress Disorder (PTSD)
What is being tested?: Prazosin and Naltrexone
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteUnited States
Study dates: 3 Mar 2015to 10 Oct 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Veteran of the U.S. military or National Guard Reserve.
Current AUD by DSM-5 criteria.
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).
At least mild alcohol craving as assessed by the Pennsylvania Alcohol Craving Scale (PACS; score > 10) at baseline.
Age 18-80.
English fluency and literacy.

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Trying or planning to try to cut down on or abstain from alcohol.
Good general medical health.
Capable of giving informed consent.

Who cannot join

Uncontrolled psychiatric disorder with psychotic symptoms or cognitive impairment.
If taking psychiatric medication, NOT on a stable dose for at least 30 days prior to randomization.
Any suicidal ideation in the past 7 days, plan or intent past 6 months, or any suicide attempt past year.
Homicidal ideation with plan and intent in the past 30 days.
Patient Health Questionnaire-9 (PHQ-9) endorsement of hopelessness or self-harm/SI and/or sum scale score ≥ 19.
Any use of prazosin or naltrexone past 30 days.

Show all 15Show fewer

Currently taking disulfiram or acamprosate OR planning to take any of these medications (including prazosin or naltrexone) during the study.
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.
Significant acute or chronic medical illness
Preexisting hypotension (sys <100) or orthostatic hypotension (systolic drop of > 20 mmHg; after two minutes of standing, or any drop with dizziness).
Allergy or previous adverse reaction to naltrexone, prazosin, quinazolines, or other α-1 adrenergic blockers or use of other α -1 adrenergic blocker.
Women who are pregnant, breastfeeding, or of childbearing potential and not using a contraceptive method judged by the investigator to be effective.
Legal involvement that could interfere with study participation, including being court ordered for treatment.
Signs or symptoms of withdrawal at time of initial consent.
Any participation in an experimental drug study or any addiction study past 30 days.

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Puget Sound Healthcare System
Seattle, Washington, 98108

Other trials in United States

About this study

Official title: Effect of Prazosin and Naltrexone on Personalized Script-Induced Alcohol Craving in Individuals With Alcohol Use Disorders With and Without Comorbid PTSD

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.

Read the detailed description

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: Alcohol Use Disorder, Posttraumatic Stress Disorder (PTSD)
Being tested: Prazosin, Naltrexone, Placebo (Prazosin), Placebo (Naltrexone)
Keywords: 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
Medical subject headings: Alcoholism, Stress Disorders, Post-Traumatic, Alcohol Drinking, Drinking Behavior, Substance-Related Disorders, Behavior, Addictive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PrazosinDrug
Also called Minipress
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
NaltrexoneDrug
Naltrexone Dosing Days 1-42: 50mg @ 9PM
Placebo (Prazosin)Drug
Also called Placebo
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)Drug
Also called Placebo
Placebo Dosing Days 1-42: 50mg @ 9PM

Study groups in NCT02322047
Study group	Role	What they receive
Praz/Nal	Experimental	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. Receives: Drug: Prazosin; Drug: Naltrexone
Praz/Pl	Active comparator	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. Receives: Drug: Prazosin; Drug: Placebo (Naltrexone)
Nal/Pl	Active comparator	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. Receives: Drug: Naltrexone; Drug: Placebo (Prazosin)
Pl/Pl	Placebo comparator	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. Receives: Drug: Placebo (Prazosin); Drug: Placebo (Naltrexone)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD)
PDD was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption from 90 days prior to their baseline visit until the day before their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Measured: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD)
PHDD was calculated based on self-reported drinking history collected via Form-90. Heavy drinking days were defined as days when participants consumed 4 or more drinks for females and 5 or more drinks for males. Form-90 was completed by participants in the baseline and last visit. Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PHDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Measured: Visit 2 (baseline) and Visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS)
Alcohol craving was assessed in visit 2 (baseline) and the last visit (visit 8) using the Pennsylvania Alcohol Craving Scale (PACS). The PACS had 5 questions, where each question had six options presented in Likert Scales from 0 to 6, with 0 being the least and 6 being the highest possible option, thus the possible minimum and maximum values are 0 and 30, respectively. Higher scores mean higher craving. This outcome measures the change in PACS scores between visits 2 and 8 (visit 8 PACS score - visit 2 PACS score). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Measured: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.

Secondary outcomes (1)

Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2)
Average drinks per day of drinking was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome reports the change in the mean drinks between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Measured: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Mar 201510 Oct 2018

First posted22 Dec 2014 (estimated)
Study start3 Mar 2015
Primary completion10 Oct 2018
Study completion10 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (14)Papers the sponsor has linked to this study.
Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 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.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02322047
Sponsor's protocol ID: W81XWH-14-1-0025
Acronym: PaN
Status last verified: Dec 2020
First submitted: 17 Dec 2014
Last updated: 29 Dec 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 2808725
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.
PubMed 7966505
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.
PubMed 10914288
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.
PubMed 12444358
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.
PubMed 11793578
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.
PubMed 12625430
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.
PubMed 16019979
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.
PubMed 16002033
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.
PubMed 16637948
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.
PubMed 16938074
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.
PubMed 16788998
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.
PubMed 16929503
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.
PubMed 17597132
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.
PubMed 17098370

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Prazosin and Naltrexone on Personalized Script-Induced Alcohol Craving in Individuals With Alcohol Use Disorders With and Without Comorbid PTSD
ClinicalTrials.gov ID: NCT02322047
Acronym / sponsor ID: PaN / W81XWH-14-1-0025
Conditions: Alcohol Use Disorder, Posttraumatic Stress Disorder (PTSD)
Keywords: Alcohol Drinking, Craving, Drinking Behavior, Prazosin, Naltrexone, Adrenergic Alpha-1 Receptor Antagonists, Adrenergic Antagonists, Adrenergic Alpha-Antagonists
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Seattle Institute for Biomedical and Clinical ResearchUniversity, hospital or other
Collaborators: United States Department of Defense, VA Puget Sound Health Care System
Study start: 3 Mar 2015 (actual)
Primary completion: 10 Oct 2018 (actual)
Study completion: 10 Oct 2018 (actual)
First posted: 22 Dec 2014 (estimated)
Results: Posted 29 Dec 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4
Model description: 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.

Arm	Type	Receives
Praz/Nal	Experimental	Drug: Prazosin, Drug: NaltrexonePrazosin 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.
Praz/Pl	Active comparator	Drug: Prazosin, Drug: Placebo (Naltrexone)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.
Nal/Pl	Active comparator	Drug: Naltrexone, Drug: Placebo (Prazosin)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.
Pl/Pl	Placebo comparator	Drug: Placebo (Prazosin), Drug: Placebo (Naltrexone)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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Veteran of the U.S. military or National Guard Reserve.
Current AUD by DSM-5 criteria.
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).
At least mild alcohol craving as assessed by the Pennsylvania Alcohol Craving Scale (PACS; score > 10) at baseline.
Age 18-80.

Key exclusion criteria (15 listed)

Uncontrolled psychiatric disorder with psychotic symptoms or cognitive impairment.
If taking psychiatric medication, NOT on a stable dose for at least 30 days prior to randomization.
Any suicidal ideation in the past 7 days, plan or intent past 6 months, or any suicide attempt past year.
Homicidal ideation with plan and intent in the past 30 days.
Patient Health Questionnaire-9 (PHQ-9) endorsement of hopelessness or self-harm/SI and/or sum scale score ≥ 19.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PrazosinAlso: MinipressPrazosin 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	Drug	Praz/Nal, Praz/Pl
NaltrexoneNaltrexone Dosing Days 1-42: 50mg @ 9PM	Drug	Nal/Pl, Praz/Nal
Placebo (Prazosin)Also: PlaceboPlacebo 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	Drug	Nal/Pl, Pl/Pl
Placebo (Naltrexone)Also: PlaceboPlacebo Dosing Days 1-42: 50mg @ 9PM	Drug	Pl/Pl, Praz/Pl

Primary outcome

Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD)
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
PDD was calculated based on self-reported drinking history collected via Form-90. Drinking days were defined as days when participants consumed alcohol. Form-90 was completed by participants in visit 2 (baseline) and visit 8 (last visit). Form-90 collected in the baseline visit recorded participants' alcohol consumption from 90 days prior to their baseline visit until the day before their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD)
Time frame: Visit 2 (baseline) and Visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
PHDD was calculated based on self-reported drinking history collected via Form-90. Heavy drinking days were defined as days when participants consumed 4 or more drinks for females and 5 or more drinks for males. Form-90 was completed by participants in the baseline and last visit. Form-90 collected in the baseline visit recorded participants' alcohol consumption 90 days prior to their baseline visit. Form-90 collected in the last visit recorded participants' alcohol consumption from baseline until the day before their last visit. This outcome measures changes in PHDD between visit 8 and visit 2. Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.
Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS)
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.
Alcohol craving was assessed in visit 2 (baseline) and the last visit (visit 8) using the Pennsylvania Alcohol Craving Scale (PACS). The PACS had 5 questions, where each question had six options presented in Likert Scales from 0 to 6, with 0 being the least and 6 being the highest possible option, thus the possible minimum and maximum values are 0 and 30, respectively. Higher scores mean higher craving. This outcome measures the change in PACS scores between visits 2 and 8 (visit 8 PACS score - visit 2 PACS score). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days. The outliers were due to scheduling difficulties.

1 secondary outcome

Change in Mean Drinks Per Day of Drinking (Visit 8 - Visit 2)
Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.

Results and safety

Results posted to the registry on 29 Dec 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Praz/Nal	8	6
Praz/Pl	7	6
Nal/Pl	7	6
Pl/Pl	9	7

Primary outcome: Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD)

Time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.. Least squares mean (Standard Error). Unit: percentage of drinking days

Measure	Praz/Nal n = 7	Praz/Pl n = 7	Nal/Pl n = 7	Pl/Pl n = 8
Value	-37 (10)	-9 (10)	-14 (10)	-15 (9)

Population analysed: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.

Primary outcome: Change in Percent Heavy Drinking Days (PHDD) (Visit 8 PHDD - Visit 2 PHDD)

Time frame: Visit 2 (baseline) and Visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.. Least squares mean (Standard Error). Unit: percentage of heavy drinking days

Measure	Praz/Nal n = 7	Praz/Pl n = 7	Nal/Pl n = 7	Pl/Pl n = 8
Value	-38 (17)	-8 (17)	-7 (17)	-13 (16)

Population analysed: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.

Primary outcome: Change in Alcohol Craving (Visit 8 PACS - Visit 2 PACS)

Measure	Praz/Nal n = 7	Praz/Pl n = 7	Nal/Pl n = 7	Pl/Pl n = 8
Value	-10.5 (2.4)	-4.6 (2.4)	-4.3 (2.4)	-3.5 (2.4)

Population analysed: Only participants who completed the study or had an intention to treat (ITT) were included in analyses.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Participants went through 8 in-person visits (screening, baseline, and visits 3 to 8). Adverse events were collected after the baseline visit, the visit where participants were randomized and received medications, through 3 safety calls and 6 visits (visits 3 to 8). There was one safety call after the baseline visit, visit 3, and visit 4. Depending on whether a participant completed the study or not, adverse events were collected from 1 to 11 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Praz/Nal	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Praz/Pl	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Nal/Pl	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Pl/Pl	0 of 9 (0%)	3 of 9 (33.3%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 2808725Berk 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.
Background: PubMed 7966505Simpson 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.
Background: PubMed 10914288McCann 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.
Background: PubMed 12444358Simpson 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.
Background: PubMed 11793578Simpson 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.
Background: PubMed 12625430Simpson 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.
Background: PubMed 16019979Comtois 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.
Background: PubMed 16002033Simpson 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.
Background: PubMed 16637948Dobie 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.
Background: PubMed 16938074Bowen 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.
Background: PubMed 16788998Kaysen 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.
Background: PubMed 16929503Simpson 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Tracy Simpson, Ph.D. principal investigator

VA Puget Sound Health Care System

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Percent Drinking Days (PDD) (Visit 8 PDD - Visit 2 PDD) (time frame: Visit 2 (baseline) and visit 8 (last visit). Per the protocol, visit 8 is scheduled to occur 42 days (± 7days) after visit 2. In reality, visit 8 occurred 35 to 76 days after visit 2 with the average of 45 days due to scheduling difficulties.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02322047, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2020.