Clinical trial NCT00623506: Adjunctive Pregnenolone in Veterans With Mild TBI
Official title: Adjunctive Pregnenolone in Veterans With Mild TBI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: TBI
Pregnenolone
Cognition
Lead sponsor: Durham VA Medical Center
Sponsor class: FED
First posted: 2008-02-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: See brief summary

Eligibility criteria: Inclusion Criteria:

1. 18-55 years of age, any ethnic group, either sex
2. History of mild TBI since September 2001. TBI occurring at age 18 or older.
3. We will adhere to the operational definition of mild TBI suggested by the World Health Organization Task Force (Holm et al.2005), with the exception of the Glasgow Coma Scale Score criteria (not available for these participants).
4. Ability to participate fully in the informed consent process.
5. No anticipated need to alter medications for the 10-week duration of the study.

Exclusion Criteria:

1. For this pilot study, we will exclude patients who report a history of seizures.
2. Serious unstable medical illness. History of cerebrovascular accident, prostate, uterine, or breast cancer. Use of oral contraceptives or other hormonal supplementation such as estrogen.
3. Current active suicidal and/or homicidal ideation, intent or plan.
4. Concomitant medications for medical conditions will be addressed on a case-by-case base and determined if exclusionary.
5. Current DSM-IV (Diagnostic and Statistical Manual, Fourth Edition) diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than TBI.
6. Female patients who are pregnant or breast-feeding.
7. Known allergy to study medication.

Primary outcomes:
measure: Brief Assessment of Cognition in Affective Disorders (BAC-A)
timeFrame: Week 2, Week 10
Secondary outcomes:
measure: Clinician Administered PTSD Scale (CAPS)
timeFrame: Week 2, Week 10
measure: Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: Week 2, Week 10
Other outcomes:
Locations:
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
Study officials:
affiliation: Durham VAMC
name: Christine E Marx, MD, MA
role: PRINCIPAL_INVESTIGATOR
References: