Intensive 7-day Treatment for PTSD Combining Ketamine With Exposure Therapy
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Ketamine; Midazolam
Intervention description: Prolonged exposure therapy combined with a single infusion of 0.50 mg/kg/hour for 40 min on day 2.; Prolonged exposure therapy combined with a single infusion of 0.045 mg/kg/hour for 40 min on day 2.
Intervention MeSH terms: Midazolam; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: PTSD

Summary:

      The purpose of this study is to combine a single infusion of Ketamine with 7-days of trauma
      focus psychotherapy to relieve post traumatic stress disorder (PTSD) symptoms more
      effectively. This treatment has the potential to produce a significant therapeutic effect
      that otherwise would take months to occur.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between the ages of 21-75 years. This age range was chosen to fit with
             prior samples in which no adverse effects of ketamine have been observed. Adults in
             the 18-20 ranges have been eliminated because previous experience indicates that they
             often lack the maturity to participate effectively in similar protocols. Females will
             be included if they are not pregnant and agreed to utilize a medically accepted birth
             control method (to include oral, injectable, or implant birth control, condom,
             diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner
             with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.

          -  Able to provide written informed consent according to Yale HIC guidelines.

          -  Able to read and write English as a primary language.

          -  Diagnosis of PTSD, as determined by the Clinician Administered PTSD Scale (CAPS-5)
             (Weathers et al., 2013).

          -  Must have a score of 50 or higher on the Clinician-Administered PTSD Scale (CAPS-5) at
             screening.

          -  No more than mild Traumatic Brain Injury (TBI) according to a modified version of the
             Brief TBI Screen (Schwab, et al., 2006).

          -  Must not have a medical/neurological problem or use medication that would render
             ketamine unsafe by history or medical evaluation.

        Exclusion Criteria:

          -  Patients with a diagnostic history of bipolar disorder, schizophrenia or
             schizoaffective disorder or currently exhibiting psychotic features as determined by
             the Structured Clinical Interview for DSM (SCID) (First, et al. 2010); dementia or
             suspicion thereof, are excluded. Other DSM Axis I disorders are permitted as long as
             they are not considered primary disorders.

          -  Patients with a history of antidepressant-induced hypomania or mania as determined by
             open-ended psychiatric interview.

          -  Serious suicide or homicide risk, as assessed by evaluating clinician; A serious
             suicide risk will be considered an inability to control suicide attempts, imminent
             risk of suicide in the investigator's judgment, or a history of serious suicidal
             behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS)
             (Posner et al., 2011) as either (1) one or more actual suicide attempts in the 3 years
             before study entry with the lethality rated at 3 or higher, or (2) one or more
             interrupted suicide attempts with a potential lethality judged to result in serious
             injury or death.

          -  Substance abuse or dependence during the 6 months prior to screening as determined by
             the Structured Clinical Interview for DSM (SCID).

          -  Any significant history of serious medical or neurological illness.

          -  Any signs of major medical or neurological illness on examination or as a result of
             electrocardiogram (ECG) screening or laboratory studies.

          -  Lifetime history of psychoactive substance or alcohol dependence or substance or
             alcohol abuse (other than nicotine or caffeine abuse), or drinking more than 5
             drinks/week during the last year.

          -  Abnormality on physical examination. A subject with a clinical abnormality may be
             included only if the study physician considers the abnormality will not introduce
             additional risk factors and will not interfere with the study procedure.

          -  A positive pre-study (screening) urine drug screen or, at the study physician's
             discretion on any drug screens given before the scans.

          -  Pregnant or lactating women or a positive urine pregnancy test for women of
             child-bearing potential at screening or prior to any imaging day.

          -  Positive HIV or Hepatitis B tests. This test will take place at the screening visit.
             Subjects will be invited back to the Yale Depression Research Program either for their
             next study visit or for a HIV/Hep debriefing session. A study physician will inform
             them in person of the results. They will be given access to counselling and advised of
             the appropriate next steps.

          -  Has received either prescribed or over-the-counter (OTC) centrally active medicine or
             herbal supplements within 60 days of enrollment into the study. Subjects who have
             taken OTC medication or herbal supplements may still be entered into the study, if, in
             the opinion of the principal/co-investigator, the medication received will not
             interfere with the study procedures or compromise safety.

          -  Any history indicating learning disability, mental retardation, or attention deficit
             disorder.

          -  Known sensitivity to ketamine.

          -  Body circumference of 52 inches or greater.

          -  Body weight of 250 pounds or greater.

          -  History of claustrophobia.

          -  Presence of cardiac pacemaker or other electronic device or ferromagnetic metal
             foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening
             questionnaire.

          -  Donation of blood in excess of 500 mL within 56 days prior to dosing.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.