Adjunctive Pregnenolone in Veterans With Mild TBI

NCT ID: NCT00623506

Last Updated: 2013-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2012-11-30

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

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Pregnenolone

Group Type: ACTIVE_COMPARATOR

Pregnenolone

Intervention Type: DRUG

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)

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Durham VA Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine E Marx, MD, MA

Role: PRINCIPAL_INVESTIGATOR

Durham VAMC

Locations

Durham VA Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

VA IRB# 01209

Identifier Type: -

Identifier Source: secondary_id

VA IRB# 01209

Identifier Type: -

Identifier Source: org_study_id