Prazosin and Naltrexone (PaN) Study for Veterans With Alcohol Use Disorders
Condition: Alcohol Use Disorder; Posttraumatic Stress Disorder (PTSD)
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Alcohol Drinking; Stress Disorders, Post-Traumatic
Intervention: Prazosin; Naltrexone; Placebo (Prazosin); Placebo (Naltrexone)
Intervention description: 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 Dosing Days 1-42: 50mg @ 9PM; 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 Dosing Days 1-42: 50mg @ 9PM
Intervention MeSH terms: Prazosin; Naltrexone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Investigator, Outcomes Assessor)
Masking description: No study staff, including the participants, will know which condition the participants are in. Only the Research Pharmacist will know the participants' conditions.
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
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; Substance Abuse; Addiction; Alcohol Addiction; Substance Addiction; Substance Dependence

Summary:

      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.
    

Eligibility criteria:

        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.