Adjunctive Pregnenolone in Veterans With Mild TBI

Not Applicable

Completed

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Placebo; Drug: Pregnenolone

• Registration Number: NCT00623506
• Lead Sponsor: Durham VA Medical Center

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

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-02-15
• Study First Submitted QC: 2008-02-25
• Study First Posted: 2008-02-26
• Primary Completion: 2009-08
• Study Completion: 2012-11
• Results First Submitted: 2013-03-05
• Status Verified: 2013-05
• Results First Submitted QC: 2013-05-13
• Last Update Submitted: 2013-05-13
• Results First Posted: 2013-06-20
• Last Update Posted: 2013-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Placebo
1	Pregnenolone	Pregnenolone

Primary Outcome Measures

Name	Time	Method
Brief Assessment of Cognition in Affective Disorders (BAC-A)	Week 2, Week 10	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).

Secondary Outcome Measures

Name	Time	Method
Clinician Administered PTSD Scale (CAPS)	Week 2, Week 10	Mean change scores (Week 2 minus Week 10) in posttraumatic stress disorder symptoms. Scores may range from 0 (no symptoms) to 136 (severe symptoms; score of 136 is based on the first 17 CAPS items administered).; A reduced CAPS score indicates a reduction in (improvement) PTSD symptoms, while an increase in CAPS score indicates an increase (worsening) in PTSD symptoms.
Quick Inventory of Depressive Symptomatology (QIDS)	Week 2, Week 10	The QIDS total scores range from 0 to 27. Total score is obtained by adding the scores for each of the nine symptom domains of the DSM-IV Major Depressive Disorder (MDD) criteria: depressed mood,loss of interest or pleasure,concentration/decision making,self-outlook,suicidal ideation, energy/fatigability,sleep,weight/appetite change,and psychomotor changes. Each item is rated 0-3 (0=least or no severity, 3=greatest severity).

Trial Locations

Locations (1)

Durham VA Medical Center; 🇺🇸 Durham, North Carolina, United States