Adjunctive Pregnenolone in Veterans With Mild TBI

Traumatic Brain Injury Clinical Trial

Official title:

Adjunctive Pregnenolone in Veterans With Mild TBI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00623506
• Other study ID #: VA IRB# 01209
• Secondary ID: VA IRB# 01209
• Status: Completed
• Phase: N/A
• First received: February 15, 2008
• Last updated: May 13, 2013
• Start date: January 2008
• Est. completion date: November 2012

Study information

• Verified date: May 2013
• Source: Durham VA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

See brief summary

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2012
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Traumatic Brain Injury

Intervention

Drug:
• Pregnenolone
Placebo for two weeks (during placebo lead-in), then: Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)
• Placebo
Placebo for two weeks (placebo lead in), then: Placebo equivalent to Pregnenolone arm: 100 mg in divided doses (50 mg, PO, BID) Placebo equivalent to Pregnenolone arm: 300 mg in divided doses (150 mg, PO, BID) Placebo equivalent to Pregnenolone arm: 500 mg in divided doses (250 mg, PO, BID)

Locations

Country	Name	City	State
United States	Durham VA Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Durham VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brief Assessment of Cognition in Affective Disorders (BAC-A)	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).	Week 2, Week 10	No
Secondary	Clinician Administered PTSD Scale (CAPS)	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.	Week 2, Week 10	No
Secondary	Quick Inventory of Depressive Symptomatology (QIDS)	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).	Week 2, Week 10	No