Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol
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|ClinicalTrials.gov Identifier: NCT01013870|
Recruitment Status : Terminated (inability to recruit adequate numbers of subjects)
First Posted : November 16, 2009
Results First Posted : November 17, 2016
Last Update Posted : January 9, 2017
|First Submitted Date ICMJE||November 13, 2009|
|First Posted Date ICMJE||November 16, 2009|
|Results First Submitted Date ICMJE||August 3, 2016|
|Results First Posted Date ICMJE||November 17, 2016|
|Last Update Posted Date||January 9, 2017|
|Study Start Date ICMJE||February 2010|
|Actual Primary Completion Date||March 2015 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury. [ Time Frame: 3 months after injury ]
The Rivermead Post-Concussive Symptoms Questionnaire (RPQ) is a 16-item self-report measure of the presence and severity of the 16 most commonly reported post-concussive symptoms found in the literature. The scale compares any current symptoms to pre-injury symptom levels to account for potential symptom exacerbation due to TBI. The range of scores is 0-64. Values for each of the 16 items include 0 (not experienced at all), 1 (no more of a problem than before the injury), 2 (mild problem), 3 (moderate problem), 4 (severe problem). The total score was a summation of symptoms that represented new symptom onset or an exacerbation of a symptom present pre-injury. (King, N.S., Crawford, S., Wenden, F.J., Moss, N.E., & Wade, D.T. . The Rivermead Post Concussion Symptoms Questionnaire: A Measure of Symptoms Commonly Experiences after Head Injury and its Reliability. Journal of Neurology 242: 587-92.)
|Original Primary Outcome Measures ICMJE
||Subjects with mild traumatic brain injury (MTBI) treated with atorvastatin for 7 days after MTBI will show a significant improvement in outcome, as measured by the Rivermead Post-Concussion Symptoms Questionnaire, administered at 3 months after injury. [ Time Frame: 3 months after injury ]|
|Change History||Complete list of historical versions of study NCT01013870 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol|
|Official Title ICMJE||The Mission Connect Mild TBI Translational Research Consortium's Integrated Clinical Protocol|
|Brief Summary||The purpose of this study is to improve the ability to diagnose problems after mild traumatic brain injury (MTBI) and to test a drug that may improve the outcome from these injuries. Of the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in the United States, as many as 75% sustain a mild TBI which can cause long-term or permanent impairments/disabilities in a significant proportion of patients. In addition, traumatic brain injury has become a signature injury of the wars in Iraq and Afghanistan. For people with these injuries, it is difficult to determine whether symptoms are due to the head injury or another condition, such as Post-traumatic Stress Disorder. In this project, there are 3 observational studies that involve testing of mental functions and behavior, imaging of the brain with special x-ray procedures, and blood samples to look at glandular function, which may be affected by head injury. A fourth study is a test of a drug, atorvastatin, which may provide protection for injured brain cells and improve outcome. By collecting and analyzing the information from these tests, it will be possible to make the process of diagnosing mild TBI or post traumatic stress disorder (PTSD) more precise, and also to see if atorvastatin is a helpful drug for patients with MTBI.|
Of the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in the United States, as many as 75% sustain a mild TBI (MTBI) which can cause long-term or permanent impairments/disabilities in a significant proportion of patients. In addition, traumatic brain injury has become a signature injury of the wars in Iraq and Afghanistan.
One of the most difficult diagnostic problems is separating the effects of MTBI and post-traumatic stress disorder (PTSD), because signs and symptoms of these conditions often overlap. Early and accurate diagnosis of MTBI and its differentiation from both acute stress disorder (ASD) and PTSD are a major priority for military medicine due to overlap in symptoms (e.g., attention problems) and the frequent lack of external signs or even self-awareness of MTBI, especially in association with blast injury.
The major goals of this project are to improve the ability to diagnose mild traumatic brain injury (MTBI) and to test a drug, atorvastatin, which may improve outcome after MTBI. To accomplish these goals, 200 MTBI subjects and 100 orthopedic injury (OI) subjects, for comparison purposes, will be recruited for variety of clinical evaluations and a phase II drug trial. Only the MTBI subjects will participate in the phase II drug trial, and these subjects may choose to participate only in the observational studies, declining the drug trial.
Potential subjects will be identified in the Emergency Departments (EDs) of two level I trauma centers, located within a few blocks of each other in Houston, Texas. Once discharged from the ED, subjects will be enrolled and baseline procedures will be performed, including behavioral/cognitive testing, sample collection, and medication teaching, including the first dose of study drug. Subjects will be followed by phone at Day 3-4 during the 7-day dosing period of the drug trial, then with return visits for all subjects at one week, one month, three months, and six months after injury.
Investigation of acute civilian MTBI could potentially elucidate the diagnostic issues of distinguishing between MTBI, post-concussion syndrome (PCS), acute stress disorder (ASD), and post-traumatic stress disorder (PTSD) because, in the civilian setting, mild traumatic brain injuries can be characterized prospectively using advanced brain imaging, EEG, and neuropsychological assessment.
We hypothesize that in comparison with OI subjects, the MTBI group will exhibit slowing of EEG frequency, alteration of cerebral white matter microstructure on diffusion tensor imaging (DTI), and cognitive deficit within 24 hours after injury. We also hypothesize that MTBI subjects will show recovery in their EEG frequency and cognition over six months following injury despite residual white matter injury on DTI. We will also collect two plasma samples and a saliva sample, the first within 24 hr of injury (baseline) and the second at six months post-injury, for measurement of potential biomarkers and genetic studies.
Magnetoencephalography (MEG) will be used to detect and characterize focal abnormalities in neurophysiological function in subjects with MTBI diagnosed with PTSD for the purpose of distinguishing between the two. MEG is a completely non-invasive imaging modality which is able to provide information regarding focal abnormalities in the brain. MEG has been shown to be sensitive to cognitive complaints in patients with MTBI and to be more sensitive to these deficits than EEG. In addition, neurophysiological abnormalities found through testing can differentiate patients with MTBI and PTSD in some studies. Thus, we propose to explore the relationship between DTI and MEG findings which may lead to identification of more distinct, replicable patterns of brain abnormalities in subjects with PTSD and MTBI that may lead to better differentiation between these groups of patients and improve diagnostic precision, as well as from patients with a combination of both disorders.
A separate analysis is designed to examine the incidence and effects of hypopituitarism after MTBI. The incidence of hypopituitarism after MTBI is not known. However, in patients who have persistent symptoms at one year post-injury, 35% have been found to have deficiency one or more pituitary hormones. The clinical characteristics, MRI imaging results, EEG and MEG results of the patients who have pituitary deficiency will be compared to those of patients with normal pituitary function. The relationship between pituitary dysfunction and functional outcome, cognitive recovery, and resolution of PCS will be examined as well.
The final component of this protocol is a Phase II randomized clinical trial of the 200 MTBI subjects to evaluate atorvastatin (Lipitor®) as a neuroprotective agent for the treatment of MTBI. The primary endpoint for this trial is three months. This trial will examine the effects of atorvastatin, given orally in a dose of 1mg/kg (up to 80 mg) for seven days, on the development of post-concussive symptoms (PCS), PTSD symptoms, cognitive recovery, and functional outcome at 3 months post-injury, on recovery of EEG and MEG at 3 months post-injury, and on changes in DTI imaging, as well as any effects on liver function.
In conclusion, traumatic brain injury has become the signature injury of the Iraq and Afghanistan wars, and many veterans with mild TBI find their injuries overlooked and misunderstood. The goal of the Mission Connect Mild TBI Translational Research Consortium is to find answers to the challenging questions associated with the diagnosis and treatment of MTBI. The four studies in this Integrated Clinical Protocol begin that process.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||June 2015|
|Actual Primary Completion Date||March 2015 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 50 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01013870|
|Other Study ID Numbers ICMJE||W81XWH-08-2-0132|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||
|Responsible Party||Claudia Sue Robertson, Baylor College of Medicine|
|Study Sponsor ICMJE||Baylor College of Medicine|
|Collaborators ICMJE||The University of Texas Health Science Center, Houston|
|PRS Account||Baylor College of Medicine|
|Verification Date||November 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP