Neurosteroids in PTSD - Biomarkers to Therapeutics
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Post-Traumatic
Intervention: DHEA
Intervention description: Subjects will be randomized to receive a one-time oral dose of DHEA (400mg) or PBO and sustained administration of the study drug for 6 weeks. There will be a 2 week placebo lead-in period [all participants], followed by subjects continuing in the randomization block of DHEA or placebo for 6 weeks following acute administration).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a parallel-group, double-blind, placebo (PBO)-controlled, randomized Phase 2 pilot study using adjunctive dehydroxyepiandrosterone [DHEA (400 mg)] will be evaluated to establish Proof of Concept (POC) for this agent in Veterans with PTSD.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-blind, placebo (PBO)-controlled, randomized Phase 2 pilot study
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD; DHEA

Summary:

      The purpose of this research is to determine if a study medication called
      Dehydroepiandrosterone (DHEA) helps to reduce PTSD symptoms in OEF/OIF/OND Veterans. In
      addition to finding out if DHEA is effective for treating PTSD symptoms, this research seeks
      to determine if DHEA is effective in treating other symptoms, such as depression and anxiety.
      Depression and anxiety are symptoms that are frequently present in Veterans who are
      experiencing PTSD. Another purpose of this research is to takes pictures of the brain using
      magnetic resonance imaging (MRI) and blood levels of various small molecules including
      neurosteroids and also proteins, which may be affected by the study drug and/or related to
      symptoms in Veterans with PTSD. This study seeks to determine if DHEA is changed to other
      compounds after it is taken by mouth and the safety and effectiveness of DHEA in Veterans
      with PTSD. This is an "add-on" study and Veterans enrolled in the study will continue to take
      all of their current medications without any changes (also called "usual care"), and DHEA or
      a sugar pill (also called a "placebo") will then be added to their current medication
      regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  OEF/OIF/OND era Veterans

          -  PTSD diagnosis (CAPS-5 score 33).

          -  Negative pregnancy test if female.

               -  Sexually active subjects are required to use a medically acceptable form of birth
                  control if they are of childbearing potential and could become pregnant during
                  the study.

               -  A medically acceptable form of birth control includes non-hormonal intrauterine
                  devices, surgical sterilization, or double barrier methods (e.g., diaphragm with
                  contraceptive jelly, condom with contraceptive foam, cervical caps with
                  contraceptive jelly).

               -  Sexual abstinence with agreement to continue abstinence or to use a medically
                  acceptable method of contraception should sexual activity occur is permissible.

          -  Female participants must have had a normal mammogram within the last year (if older
             than 40)

          -  Female participants must have had a normal pelvic exam within the last year

          -  No change in medications less than 4 weeks before baseline assessment

          -  No anticipated need to alter medications for PTSD for the 6-week study duration (as
             determined by study physician's review of records and/or discussion with prescribing
             physician).

          -  Ability to fully participate in the informed consent process

        Exclusion Criteria:

          -  Unstable medical or neurological illness, including seizures, renal impairment or CVA
             and inability to participate in neuroimaging (fMRI).

          -  Use of oral contraceptives or other hormonal supplements, as it is unclear if DHEA
             metabolism to other neurosteroids such as estradiol may potentially impact
             contraceptive efficacy.

          -  Significant suicidal or homicidal ideation.

          -  Current DSM-5 diagnosis of bipolar disorder, schizophrenia, or other psychotic
             disorder (including major depression with psychotic features), or cognitive disorder
             due to a general medical condition.

          -  Female patients who are pregnant or breast-feeding.

          -  Known allergy to study medication.

          -  History of moderate or severe TBI.

          -  Substance dependence within past three months, per DSM-5 criteria (excluding caffeine
             and nicotine).

          -  Abnormal prostate specific antigen (PSA; >2.5ng/ml in males age 49 or less; >4ng/ml in
             males age 50 or greater) or history of prostate cancer, breast cancer, or uterine
             cancer.

          -  A family history of prostate, breast or endometrial cancer in a first-degree relative.

          -  Presence of any factors/conditions, medical or non-medical, that may interfere with
             conduction of study assessments in the judgment of the study team.

          -  Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or
             hematologic illness, symptomatic peripheral vascular disease, or other medical
             condition or psychiatric conditions or behaviors that would compromise participation
             and/or likely to lead to worsening of symptoms during the course of the study in the
             opinion of study physician and research team.

          -  Are non-ambulatory or require the use of crutches or a walker.

          -  Taking Narcotic medications or benzodiazepines for any reason.