Adjunctive Pregnenolone in Veterans With Mild TBI

Study Summary

Mild traumatic brain injury (TBI) is common among veterans who have served in OEF/OIF (Operation Enduring Freedom in Afghanistan/Operation Iraqi Freedom) and other theatres. Delayed symptoms may occur following TBI, including cognitive symptoms (impaired attention, processing speed, executive functioning), as well as behavioral symptoms such as anxiety, depression, and irritability (Fann et al. 2004; Holsinger et al. 2002). Neuroactive steroids have neuroprotective effects in rodent models of TBI (Djebaili et al. 2005; Djebaili et al. 2004; He et al. 2004; Pettus et al. 2005; Roof et al. 1997) and the neuroactive steroid pregnenolone and its sulfated derivative also markedly enhance learning and memory in rats (Akwa et al. 2001; Flood et al. 1992; Flood et al. 1995; Vallee et al. 1997; Vallee et al. 2003). In humans, reductions in pregnenolone (George et al. 1994) and its GABAergic metabolite allopregnanolone (Uzunova et al. 1998) have been associated with depressive symptoms. Pharmacological intervention with the neuroactive steroid pregnenolone could therefore result in a multi-targeted treatment approach, potentially improving cognitive deficits as well as anxiety and depression symptoms following TBI.

Primary Outcome

Mean change scores (Week 2 minus Week 10) to assess cognitive changes. The BAC-A includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3. Mean change scores from week 2 and week 10 (Week 2 minus Week 10).

Interventions

• DRUG Placebo
• DRUG Pregnenolone