A Pilot Trial of Citicoline in Returning Veterans With Mild Traumatic Brain Injury (mTBI)
This investigation will explore the impact of 8 weeks of citicoline treatment on cognitive function, clinical state and substance use in 40 returning male and female veterans with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) symptoms.
Traumatic Brain Injury
Post-traumatic Stress Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||A Pilot Trial of Citicoline in Returning Veterans With mTBI|
- Neurocognitive Assessment Changes with Citicoline Treatment [ Time Frame: At baseline and at treatment week 4 and week 8 ] [ Designated as safety issue: No ]4-Subtest Wechsler Abbreviated Scale of Intelligence (WASI) at the baseline visit only. Measures to be administered at baseline and both follow-up visits: Hopkins Verbal Learning Test-Revised (HVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Logical Memory (LM) Subtest of the Wechsler Memory Scale-Revised (WMS-R) and Sullivan Multiple Versions, Rey-Osterreith Complex Figure (Rey-O), Stroop Color-Word Test, Trailmaking Test A & B, Controlled Oral Word Association Test (COWAT), Digit Span subtest of the WAIS-R, Digit Symbol Substitution Test (DSST), Wisconsin Card Sort Test (WCST), Go/No Go Test, Time Estimation Task (TET), and Facial Expressions of Emotion-Stimuli and Tests (FEEST).
- Clinical State Assessment Changes with Citicoline Treatment [ Time Frame: Weekly assessment & biweekly clinical scales for 8 weeks ] [ Designated as safety issue: No ]Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Hamilton Anxiety Scales (HAM-A), Positive & Negative Affect Scale (PANAS), Profile of Mood States (POMS), Barratt Impulsiveness Scale (BIS), UPPS Impulsive Behavior Scale (UPPS-P), Impulsiveness-Venturesomeness-Empathy Scale (IVE), State/Trait Inventory (STAI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Beck Scale for Suicidal Ideation (BSS), Beck Anxiety Inventory (BAI), Frontal Systems Behavior Scale (FrSBe), Alcohol Use Disorders Identification Test (AUDIT), Cannabis Use Disorders Identification Test-Revised (CUDIT-R), National Center for PTSD 17-item checklist (PCL), Neurobehavioral Symptom Inventory (NSI), Combat Exposure Scale (CES), & Clinician Administered PTSD Scale (CAPS).
- Functional MRI and Diffusion Tensor Imaging Changes with Citicoline Treatment [ Time Frame: At baseline and at treatment week 8 ] [ Designated as safety issue: No ]All functional MR imaging (fMRI) will be performed on the 3 Tesla (3T) scanner retrofitted with a whole body echo-planar coil with a TIM upgrade. The challenge paradigms will be a Masked Affect paradigm, the Multi-Source Interference Task (MSIT), and a Trauma-Related Emotional Counting Stroop. In addition, diffusion tensor imaging (DTI) will be acquired to assess white matter microstructure integrity by measuring fractional anisotropy (FA) and mean diffusivity (MD).
- Magnetic Resonance Spectroscopy Changes with Citicoline Treatment [ Time Frame: At baseline and at treatment week 8 ] [ Designated as safety issue: No ]Proton magnetic resonance spectroscopy (MRS) will be acquired at 3 Tesla using both single voxel and chemical shift imaging (CSI) techniques in order to assess brain metabolite levels pre and post treatment.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
8-week treatment of 2,000mg/day of citicoline
2,000mg/day of citicoline taken as twice daily unit doses of 1,000 mg for the 8-week period of the clinical trial
Other Name: Citicoline Sodium
|Placebo Comparator: Placebo||
Placebo arm of single-blind study
Traumatic brain injury (TBI) remains a major cause of death and disability within the United States. Approximately 1.4 million individuals sustain a TBI each year, and currently, more than 5.3 million Americans or 3% of the general population live with disabilities associated with a TBI, resulting in enormous financial, physical and psychosocial burdens to the patients, their families and society. The issue of TBI has never been more salient, as it is now labeled the "signature wound" of the current conflict in Iraq and Afghanistan. Although TBI-related fatalities have decreased dramatically as a result of medical advances and improvements in protective gear, many soldiers are instead returning from war with symptoms of mild TBI (mTBI). Recent surveys suggest that of the 2 million military personnel deployed to Iraq or Afghanistan, 2,700 have endured moderate to severe TBI, but it is estimated that up to 400,000 have sustained mTBI. The high prevalence of less severe brain injuries has necessitated a shift in rehabilitation efforts to focus on diagnosing and treating soldiers with mTBI symptomatology. Soldiers with less severe injuries have historically been treated superficially and returned to duty, but many mTBI survivors live with residual disabilities, have unmet care needs, and can have difficultly returning to their daily lives. This is in part due to the fact that the majority of mTBI research has been conducted only in civilian populations. Patients with non-blast-related mTBI generally have been shown to fully recover shortly after injury. However, 10-20% of blast-related mTBI patients continue to report post-concussive symptoms after this initial period, and recent estimates suggest that 44-50% of mTBI victims experience 3 or more symptoms one year post-injury, suggesting that blast-related mTBI may have a unique course of recovery as compared to other types of mTBI injury.
Patients with mTBI often experience a variety of symptoms including headache, dizziness, fatigue, irritability, depression, anxiety, insomnia, reduced alcohol tolerance, and problems with cognitive function. In acute stages, cognitive deficits may affect multiple domains and be severe enough to interfere with everyday activities. As combat intensity simultaneously elevates the risk for physical and psychological injuries, many mTBI victims are comorbid for psychiatric disorders including PTSD. According to the RAND study of post-Iraqi military deployment, over one-third of soldiers with mTBI were also diagnosed with PTSD or depression. A number of PTSD symptoms are similar and tend to overlap with the symptoms of mTBI including difficulties with attention, learning, memory, and executive function. Furthermore, research suggests that the cognitive impairments and neurobiological alterations associated with mTBI negatively affect treatment outcomes. In a recent study of blast vs. non-blast mTBI injuries, no differences were noted between the groups on post-concussive symptoms, however, PTSD symptoms accounted for a substantial amount of variance in the post-concussive symptom reports, suggesting that the PTSD accounted for a large percentage of their presenting symptoms. Given the recent influx of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans seeking treatment following head trauma, it is increasingly important to develop new treatment strategies that address PTSD and mTBI comorbidity.
The proposed investigation will explore the impact of 8 weeks of citicoline treatment on cognitive function, clinical state and substance use in 40 returning male and female veterans with mTBI and PTSD symptoms. The investigators hypothesize that returning veterans with mTBI who receive citicoline will demonstrate improvements in cognitive performance relative to their own pre-treatment levels as well as to those randomized to placebo. Specifically, the investigators expect the greatest improvement on frontal/executive measures following treatment with citicoline. In addition, the investigators also hypothesize that 8 weeks of treatment with citicoline will result in a reduction of PTSD-related symptoms, comorbid substance use and improvements in clinical state measures relative to both pre-treatment levels and those randomized to receive placebo. Given the relationship between cognitive function and clinical state, the investigators expect a primary improvement in cognitive function will likely precede the expected improvement of PTSD-related symptoms.
|Contact: Kelly A Sagar, B.A.||email@example.com|
|Contact: Mary K Dahlgren, B.A.||firstname.lastname@example.org|
|United States, Massachusetts|
|McLean Hospital Brain Imaging Center||Recruiting|
|Belmont, Massachusetts, United States, 02478-9106|
|Principal Investigator: Staci A Gruber, Ph.D.|
|Sub-Investigator: David P Olson, M.D., Ph.D.|
|Sub-Investigator: Scott E Lukas, Ph.D.|
|Sub-Investigator: Atilla Gonenc, Ph.D.|
|Principal Investigator:||Staci A Gruber, Ph.D.||Mclean Hospital|
|Study Chair:||Scott E Lukas, Ph.D.||Mclean Hospital|