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Adjunctive Pregnenolone in Veterans With Mild TBI

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Durham VA Medical Center
ClinicalTrials.gov Identifier:
NCT00623506
First received: February 15, 2008
Last updated: May 13, 2013
Last verified: May 2013

February 15, 2008
May 13, 2013
January 2008
August 2009   (final data collection date for primary outcome measure)
Brief Assessment of Cognition in Affective Disorders (BAC-A) [ Time Frame: Week 2, Week 10 ] [ Designated as safety issue: No ]
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).
The primary endpoints will be changes in cognitive symptoms over the course of the study (BAC-A) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00623506 on ClinicalTrials.gov Archive Site
  • Clinician Administered PTSD Scale (CAPS) [ Time Frame: Week 2, Week 10 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Week 2, Week 10 ] [ Designated as safety issue: No ]
    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).
Secondary outcome measures will be PTSD symptoms (CAPS), depressive symptoms (QIDS), and other cognitive scales (CPT, Trail Making, and WCST) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Adjunctive Pregnenolone in Veterans With Mild TBI
Adjunctive Pregnenolone in Veterans With Mild TBI

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.

See brief summary

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
  • 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)

  • 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)

  • Active Comparator: 1
    Pregnenolone
    Intervention: Drug: Pregnenolone
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
November 2012
August 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00623506
VA IRB# 01209, VA IRB# 01209
Not Provided
Durham VA Medical Center
Durham VA Medical Center
Not Provided
Principal Investigator: Christine E Marx, MD, MA Durham VAMC
Durham VA Medical Center
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP