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Adjunctive Pregnenolone in Veterans With Mild TBI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00623506
Recruitment Status : Completed
First Posted : February 26, 2008
Results First Posted : June 20, 2013
Last Update Posted : June 20, 2013
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Pregnenolone Drug: Placebo Not Applicable

Detailed Description:
See brief summary

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Adjunctive Pregnenolone in Veterans With Mild TBI
Study Start Date : January 2008
Actual Primary Completion Date : August 2009
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
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 Comparator: 2
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)

Primary Outcome Measures :
  1. Brief Assessment of Cognition in Affective Disorders (BAC-A) [ Time Frame: 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 :
  1. Clinician Administered PTSD Scale (CAPS) [ Time Frame: 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.

  2. Quick Inventory of Depressive Symptomatology (QIDS) [ Time Frame: 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00623506

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United States, North Carolina
Durham VA Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Durham VA Medical Center
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Principal Investigator: Christine E Marx, MD, MA Durham VAMC
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Responsible Party: Durham VA Medical Center Identifier: NCT00623506    
Other Study ID Numbers: VA IRB# 01209
VA IRB# 01209
First Posted: February 26, 2008    Key Record Dates
Results First Posted: June 20, 2013
Last Update Posted: June 20, 2013
Last Verified: May 2013
Keywords provided by Durham VA Medical Center:
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries