Ketamine and Prolonged Exposure in PTSD
Condition: Post-traumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study aims at investigating the effectiveness of the drug, Ketamine, in combination with
      Prolonged Exposure (PE) therapy for people suffering from PTSD. Participation in the study
      includes Ketamine infusions, which occur once a week for three weeks. PE therapy sessions
      will be scheduled one day after each infusion, and may continue up to 12 weeks. After
      completely therapy, there will be two monthly follow-up assessment visits.
    

Detailed description: 
      Study location: Minneapolis VA Medical Center

      The study is an open-label interventional study designed to inform and strengthen the
      feasibility of protocol implementation on sub-anesthetic doses of intravenous Ketamine as
      augmenting strategy of standardized, manually-driven Prolonged Exposure therapy in PTSD.

      Timeline: Eligible individuals can expect their participation to last up to 5 months.
      Compensation will be given for participation per session that is attended. Potential
      participants will be provided with information about the study and asked a series of
      questions to determine if they meet basic inclusion/exclusion criteria (e.g., indicators of
      current PTSD). They will be informed that the treatment involves multiple infusions of
      sedatives at subanesthetic doses followed by PE therapy. Those interested will be scheduled
      for an in-person, baseline session.

      Voluntary informed consent will be obtained in accordance with local IRB approvals. During
      the baseline, all assessments, computer tasks, and information on treatment will be
      explained. Participants will also undergo a urine toxicology analysis during this session.
      Ketamine infusions and PE therapy appointments will be scheduled within two weeks of the
      baseline.

      The day of the infusion, patients will arrive in the morning after an overnight fast of at
      least 8 hours. An IV will be placed in the non-dominant arm for medication administration.
      Vitals will be recorded throughout the entire medication treatment. Subjects will then
      receive IV infusion of 0.5mg/Kg of ketamine hydrochloride solution over 40 minutes. The dose
      of ketamine will be calculated by ideal body weight. Any altered sensory or dissociative
      effects will be measured before and after each infusion. Vitals will be monitored for another
      hour, until all side-effects have subsided. Participants are required not to drive or use
      heavy machinery until the following morning.

      One day after the infusion, patients will come back for study assessments and Prolonged
      Exposure therapy with a VA psychologist. PE is an evidence-based psychotherapy for PTSD that
      is based on the Emotional Processing Theory of PTSD; the four components of PE are: 1)
      exposure to safe situations, objects, or people that cause distress and are avoided because
      they are trauma reminders (in vivo exposure), 2) revisiting and processing of the trauma
      memory (imaginal exposure), 3) psycho-education about trauma-related symptoms, and 4)
      breathing retraining. Session 1 includes the presentation of treatment rationale and program
      overview, information gathering, and breathing retraining. Session 2 includes education about
      common reactions to trauma, rationale for in vivo exposure, and construction of an in vivo
      exposure hierarchy. The hierarchy includes safe or low-risk activities and situations that
      were avoided because of their association with the trauma. Throughout the treatment,
      participants will be assigned homework to confront items on the hierarchy in a gradual
      fashion, working up to the most anxiety-arousing situations. During Session 3, the rationale
      for confronting the trauma memory in imagination is presented and initiation of imaginal
      exposure and processing is conducted. In this procedure, participants will be asked to close
      their eyes, visualize the trauma, and recount it aloud in the present tense for 45-60 min.
      The memory recounting will be repeated if necessary to allow total reliving of 45-60 min. The
      exposure will be audiotaped; participants will be instructed to listen daily to the tape.
      Sessions 4-10 will be conducted in a similar fashion: therapists review homework, conduct
      imaginal exposure to trauma memory for 30-45 min, discuss the imaginal exposure, and assigned
      in vivo and imaginal exposure homework. In the final session, participants summarize learning
      in treatment, discuss their progress, plans, and relapse prevention.

      Upon PE completion, participants are asked to come back for 2 follow-up sessions over two
      months. Familiar study and PTSD assessments will be administered during this time.
    

Intervention name(s): ketamine-enhanced prolonged exposure
Intervention type(s): Drug
Intervention description(s): Subjects will receive a single infusion of racemic ketamine at 0.5mg/kg (ideal body weight) for 40 minutes. The next day, patients will have a standardized prolonged exposure session which lasts approximately 90 minutes. This co-jointed intervention will be repeated for 3 weeks. Then, patients will continue with therapy sessions to complete a total of 10-12 sessions.
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Intervention model description: Open-label study
Masking: None (Open Label)
Primary purpose: Treatment