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
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Prazosin; Naltrexone; Placebo (Prazosin); Placebo (Naltrexone)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Minipress; Placebo; Placebo
Intervention MeSH terms: Prazosin; Naltrexone
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)
Primary purpose: Treatment
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