Stress Reactivity in Veterans Receiving Pharmacological Treatment for PTSD and Alcohol Dependence
Condition: Post-traumatic Stress Disorder; Alcohol Dependence
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      Method: This study is designed as an accompaniment to an already funded study - a 12-week
      treatment trial with prazosin for patients with PTSD and AD.

      The study design will consist of III phases. In phase I, all subjects will participate in
      three laboratory sessions to determine their reactivity to stress. Stress reactivity will be
      measured using: traumatic experiences, stressful non-trauma experiences and neutral
      experiences, presented randomly. Laboratory sessions will be conducted in an outpatient
      setting. Phase II is a randomized clinical trial evaluating prazosin versus placebo for 12
      weeks in a double-blind, controlled fashion in an outpatient setting. The treatment will last
      for 12 weeks and outcomes will include symptoms of PTSD and alcohol use. In phase III,
      subjects will again participate in a laboratory session. This phase of the study will be
      conducted after at least 6 weeks of treatment while patients are on medication (prazosin or
      placebo).

      Hypotheses:

      Primary: The investigators hypothesize that prazosin will be more effective than placebo in
      reducing trauma-related stress reactivity in a laboratory paradigm, particularly anxiety,
      craving for alcohol, and hormonal response, in individuals with PTSD and AD.

      Secondary: The investigators hypothesize that stress reactivity will have a moderating effect
      on treatment with prazosin, such that individuals with high levels of stress reactivity will
      have fewer heavy drinking days, a significant reduction in PTSD symptoms, and shorter time to
      relapse than individuals with low levels of stress reactivity.
    

Detailed description: 
      Specific Aim: We propose a laboratory study that will examine stress reactivity as a marker
      for treatment response to prazosin in patients with PTSD and AD.

      Background: Increasing evidence shows that PTSD and AD are both associated with abnormalities
      in stress reactivity. In PTSD, the increase in hormonal response and subjective increases in
      affective symptoms provide evidence for abnormalities in stress reactivity. In AD,
      significant increases in craving after stressful stimuli and alcohol cues point to
      abnormalities in stress response. There is increasing evidence that these laboratory
      paradigms are clinically relevant and may be useful in predicting treatment outcomes in
      patients with substance use disorders. Stress induced craving has been used as a marker for
      relapse. Individuals with greater stress reactivity have a shorter time to relapse to their
      preferred substance than individuals with lesser stress reactivity.

      Attenuation of trauma-related distress may be effective in reducing both craving and negative
      affect in individuals with PTSD and AD. In a very elegant study, Coffey and his colleagues
      (Coffey et al, 2006) found that imaginal exposure therapy was more effective than relaxation
      alone in reducing craving for alcohol after exposure to stressful imagery and alcohol cues.
      However, it should be noted that interventions such as imaginal exposure therapy target only
      symptoms of PTSD, have to be administered by highly trained professionals and have to be
      provided in specialized settings.

      We propose a laboratory study that will test whether pharmacotherapy that targets both
      symptoms of PTSD and AD can attenuate the stress response, and how the attenuation of stress
      response will affect relapse and outcome.

      Method: This study is designed as an accompaniment to an already funded study by the DOD - a
      12-week treatment trial with prazosin for patients with PTSD and AD. The current proposal
      will augment the findings from the treatment study and identify for which patients prazosin
      may be effective. It is important to note that this study is very different from the PTSD
      Coop study in that study EXCLUDES individuals with alcohol dependence. The DOD study and this
      companion study will provide answers relevant to alcohol use, alcohol relapse and drinking
      outcomes.

      The study design will consist of III phases. In phase I, all subjects will participate in
      three laboratory sessions to determine their reactivity to stress. Stress reactivity will be
      measured using: traumatic experiences, stressful non-trauma experiences and neutral
      experiences, presented randomly. Laboratory sessions will be conducted in an inpatient
      setting. Phase II is a randomized clinical trial evaluating prazosin versus placebo for 12
      weeks in a double-blind, controlled fashion in an outpatient setting. The treatment will last
      for 12 weeks and outcomes will include symptoms of PTSD and alcohol use. In phase III,
      subjects will again be admitted to an inpatient unit. This phase of the study will be
      conducted during the 12th and final week on medication while participants are still receiving
      prazosin or placebo.

      Hypotheses: Primary: We hypothesize that prazosin will be more effective than placebo in
      reducing trauma-related stress reactivity in a laboratory paradigm, particularly anxiety,
      craving for alcohol, and hormonal response, in individuals with PTSD and AD. And this will be
      a marker for treatment response to prazosin in patient with PTSD and AD.

      Secondary: We hypothesize that stress reactivity will have a moderating effect on treatment
      with prazosin, such that individuals with high levels of stress reactivity will have fewer
      heavy drinking days, a significant reduction in PTSD symptoms, and shorter time to relapse
      than individuals with low levels of stress reactivity.
    

Intervention name(s): stress
Intervention type(s): Behavioral
Intervention description(s): compare levels of stress
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: stress reactivity; PTSD; alcohol dependence; drinking; craving