The Mission Connect Mild TBI Translational Research Consortium's Integrated Clinical Protocol
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18-50 years
- •MTBI subjects: evidence of closed head injury; Glasgow Coma Score 13-15; loss of consciousness < 30 minutes; post-traumatic amnesia < 24 hours; Abbreviated Injury Score </= 3 for any body region; absence of focal lesions on head CT scan
- •Orthopedic Injury subjects: evidence of traumatic injury, other than head; Abbreviated Injury Score </= 3 for any body region
- •does not require hospitalization for injuries
- •visual acuity and hearing adequate to participate in testing
- •fluent in either English or Spanish
排除标准
- •Abbreviated Injury Score > 3 for any body region
- •any type of penetrating injury
- •history of significant pre-existing disease or systemic injuries
- •history of schizophrenia or bipolar disorder
- •blood alcohol > 200 mL/dL
- •left-handed
- •existing contraindications for MRI
- •claustrophobia
- •pregnancy
- •exclusions related to atorvastatin, including currently taking any statin drug (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin), no longer taking a statin drug but history of use within the last six months, previously taking any statin drug at any time but now discontinued due to side effects, taking any medication with known interactions with atorvastatin (cyclosporine, fibric acid derivative, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir, niacin in doses exceeding multivitamin dosage, or azole antifungals), active liver disease, history of unexplained persistent elevation of serum transaminases, and hypersensitivity to any component of atorvastatin.
研究组 & 干预措施
MTBI subjects randomized to drug
Of 200 MTBI subjects enrolled, 1:1 randomization will be used to assign half (i.e 100) to the treatment arm of the phase II drug trial of atorvastatin. These subjects will receive a daily weight-based dose of atorvastatin 1mg/kg (up to 80 mg) for seven days and started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving a placebo.
NOTE: The 100 Orthopedic Injury subjects recruited for and participating in the Observational studies are not included in the Medication study portion of this protocol.
干预措施: Atorvastatin (Drug)
MTBI subjects randomized to placebo
Of 200 MTBI subjects enrolled, 1:1 randomization will be used to assign half (i.e 100) to the placebo arm of the phase II drug trial of atorvastatin. These subjects will receive a daily dose of an inert preparation, visually indistinguishable from the active agent. They will take this preparation for seven days, started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving active drug.
NOTE: The 100 Orthopedic Injury subjects recruited for and participating in the Observational studies are not included in the Medication study portion of this protocol.
干预措施: Placebo (Drug)
结局指标
主要结局
Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury.
时间窗: 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. \[1995\]. The Rivermead Post Concussion Symptoms Questionnaire: A Measure of Symptoms Commonly Experiences after Head Injury and its Reliability. Journal of Neurology 242: 587-92.)
次要结局
- Medical Outcome Study Short Form 12 - Mental Score(3 months)
- Medical Outcome Study Short Form 12 - Physical Score(3 months after injury)
- Post-traumatic Stress Checklist - Civilian Form(3 months after injury)
- Connor Davidson Resilience Measure(3 months after injury)
- Center for Epidemiological Study Depression Scale(3 months after injury)
- Brief Visuospatial Memory Test - Revised(3 months after injury)
- Symbol Digit Modalities Test - Oral Score(3 months after injury)
- Symbol Digit Modalities Test - Written Score(3 months after injury)
研究者
Claudia Sue Robertson
Professor, Department of Neurosurgery
Baylor College of Medicine