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
  Purpose

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 Intervention
Traumatic Brain Injury
Drug: Pregnenolone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Adjunctive Pregnenolone in Veterans With Mild TBI

Resource links provided by NLM:


Further study details as provided by Durham VA Medical Center:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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).


Enrollment: 30
Study Start Date: January 2008
Study Completion Date: November 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Pregnenolone
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
Placebo
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)


Detailed Description:

See brief summary

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623506

Locations
United States, North Carolina
Durham VA Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Durham VA Medical Center
Investigators
Principal Investigator: Christine E Marx, MD, MA Durham VAMC
  More Information

No publications provided

Responsible Party: Durham VA Medical Center
ClinicalTrials.gov Identifier: NCT00623506     History of Changes
Other Study ID Numbers: VA IRB# 01209, VA IRB# 01209
Study First Received: February 15, 2008
Results First Received: March 5, 2013
Last Updated: May 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Durham VA Medical Center:
TBI
Pregnenolone
Cognition

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System

ClinicalTrials.gov processed this record on August 01, 2014