Back to resultsAdjunctive Pregnenolone in Veterans With Mild TBI
Primary Purpose
Traumatic Brain Injury
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pregnenolone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury focused on measuring TBI, Pregnenolone, Cognition
Eligibility Criteria
Inclusion Criteria:
- 18-55 years of age, any ethnic group, either sex
- History of mild TBI since September 2001. TBI occurring at age 18 or older.
- 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).
- Ability to participate fully in the informed consent process.
- No anticipated need to alter medications for the 10-week duration of the study.
Exclusion Criteria:
- For this pilot study, we will exclude patients who report a history of seizures.
- Serious unstable medical illness. History of cerebrovascular accident, prostate, uterine, or breast cancer. Use of oral contraceptives or other hormonal supplementation such as estrogen.
- Current active suicidal and/or homicidal ideation, intent or plan.
- Concomitant medications for medical conditions will be addressed on a case-by-case base and determined if exclusionary.
- 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.
- Female patients who are pregnant or breast-feeding.
- Known allergy to study medication.
Sites / Locations
- Durham VA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
Pregnenolone
Placebo
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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).
Full Information
NCT ID
NCT00623506
First Posted
February 15, 2008
Last Updated
May 13, 2013
Sponsor
Durham VA Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00623506
Brief Title
Adjunctive Pregnenolone in Veterans With Mild TBI
Official Title
Adjunctive Pregnenolone in Veterans With Mild TBI
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Durham VA Medical Center
4. Oversight
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
TBI, Pregnenolone, Cognition
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Pregnenolone
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Pregnenolone
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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 Measure Information:
Title
Brief Assessment of Cognition in Affective Disorders (BAC-A)
Description
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).
Time Frame
Week 2, Week 10
Secondary Outcome Measure Information:
Title
Clinician Administered PTSD Scale (CAPS)
Description
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.
Time Frame
Week 2, Week 10
Title
Quick Inventory of Depressive Symptomatology (QIDS)
Description
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).
Time Frame
Week 2, Week 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18-55 years of age, any ethnic group, either sex
History of mild TBI since September 2001. TBI occurring at age 18 or older.
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).
Ability to participate fully in the informed consent process.
No anticipated need to alter medications for the 10-week duration of the study.
Exclusion Criteria:
For this pilot study, we will exclude patients who report a history of seizures.
Serious unstable medical illness. History of cerebrovascular accident, prostate, uterine, or breast cancer. Use of oral contraceptives or other hormonal supplementation such as estrogen.
Current active suicidal and/or homicidal ideation, intent or plan.
Concomitant medications for medical conditions will be addressed on a case-by-case base and determined if exclusionary.
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.
Female patients who are pregnant or breast-feeding.
Known allergy to study medication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine E Marx, MD, MA
Organizational Affiliation
Durham VAMC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Durham VA Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Adjunctive Pregnenolone in Veterans With Mild TBI
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