Neuroactive Steroids and Traumatic Brain Injury (TBI) in OEF/OIF Veterans
Status:
Completed
Trial end date:
2016-02-01
Target enrollment:
Participant gender:
Summary
Purpose: Mild traumatic brain injury (TBI) is extremely common among Operation Enduring
Freedom/Operation Iraqi Freedom (OEF/OIF) era Veterans. Mild TBI is frequently accompanied by
post-traumatic stress disorder (PTSD) and depression symptoms, co-occurring disorders that
contribute to increased disability and decreased quality of life. Neuroactive steroids (NS)
represent promising pharmacological candidates for intervention for these diverse symptom
domains, since a number of these molecules demonstrate pronounced neuroprotective and
neurotrophic properties. The NS pregnenolone (PREG) is a logical therapeutic option, since it
enhances learning and memory and also increases myelination in rodent models. Further,
decreases in PREG have been associated with depressive symptoms, and PREG is also metabolized
to allopregnanolone (ALLO), an anxiolytic downstream NS that is decreased in PTSD. ALLO also
enhances neurogenesis in rodents. The investigators thus propose an randomized controlled
trial (RCT) in OEF/OIF era Veterans with mild TBI.
Methodology: The design of this study will be randomized, placebo-controlled, double-blind.
Trial duration will be 10 weeks, consisting of a 2-week placebo lead-in period for all
subjects, followed by 8 weeks of treatment with either pregnenolone or placebo. The primary
cognitive outcome measure will be executive functioning (as assessed by the Tower of London
test), and the primary behavioral outcome measure will be PTSD Cluster D symptoms (as
assessed by the Clinician-Administered PTSD Scale, CAPS). The investigators will also
determine if PREG administration in OEF/OIF Veterans with mild TBI increases downstream ALLO
and/or other GABAergic NS levels, and the investigators will identify the specific metabolism
profile of PREG following eight weeks of treatment with this neurosteroid.
Anticipated Findings: The investigators hypothesize that treatment with PREG in OEF/OIF era
Veterans with mild TBI will significantly improve executive functioning compared to the
placebo condition. The investigators also predict that treatment with PREG will decrease
Cluster D PTSD symptoms compared to treatment with placebo.