The Future of Clinical Trials in Traumatic Brain Injury

2018 ◽  
pp. 247-256
Author(s):  
David S. Hersh ◽  
Beth M. Ansel ◽  
Howard M. Eisenberg
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
The Future

scholarly journals Progress in Clinical Neurosciences: Therapeutic Hypothermia in Severe Traumatic Brain Injury

2003 ◽  
Vol 30 (4) ◽  
pp. 307-313 ◽  
Author(s):  
David A. Zygun ◽  
Christopher J. Doig ◽  
Roland N. Auer ◽  
Kevin B. Laupland ◽  
Garnette R. Sutherland
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Severe Traumatic Brain Injury ◽  
Clinical Studies ◽  
Current Evidence ◽  
Optimal Temperature ◽  
Widespread Acceptance ◽  
The Future

Severe traumatic brain injury (sTBI) is a relatively common problem with few therapies proven effective. Despite its use for over 50 years, therapeutic hypothermia has not gained widespread acceptance in the treatment of sTBI due to conflicting results from clinical trials. This review will summarize the current evidence from animal, mechanistic and clinical studies supporting the use of therapeutic hypothermia. In addition, issues of rewarming and optimal temperature will be discussed. Finally, the future of hypothermia in sTBI will be addressed.

Clinical Trials in Traumatic Brain Injury: Lessons for the Future

2004 ◽  
Vol 16 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Egon M. R. Doppenberg ◽  
Sung C. Choi ◽  
Ross Bullock
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
The Future

scholarly journals Intraoperative hypothermia during vascular neurosurgical procedures

2009 ◽  
Vol 26 (5) ◽  
pp. E24 ◽  
Author(s):  
Raymond Choi ◽  
Robert H. Andres ◽  
Gary K. Steinberg ◽  
Raphael Guzman
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Animal Models ◽  
Mild Hypothermia ◽  
Scientific Evidence ◽  
Neurosurgical Procedures ◽  
Ischemic Damage ◽  
Intraoperative Hypothermia ◽  
Improved Outcomes

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.

scholarly journals Assessment of White Matter Injury and Outcome in Severe Brain Trauma

2012 ◽  
Vol 117 (6) ◽  
pp. 1300-1310 ◽  
Author(s):  
Damien Galanaud ◽  
Vincent Perlbarg ◽  
Rajiv Gupta ◽  
Robert D. Stevens ◽  
Paola Sanchez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
White Matter ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Unfavorable Outcome ◽  
Operating Characteristic Curve

Background Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). Methods In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n=38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. Results Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. Conclusions White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

scholarly journals The case for introducing pre-registered confirmatory pharmacological pre-clinical studies

2018 ◽  
Vol 38 (5) ◽  
pp. 749-754 ◽  
Author(s):  
Olivia Kiwanuka ◽  
Bo-Michael Bellander ◽  
Anders Hånell
Keyword(s):  
Clinical Trial ◽  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Network Analysis ◽  
Clinical Studies ◽  
Phase Iii ◽  
Phase Iii Clinical Trial ◽  
Phase Iii Clinical Trials ◽  
Experimental Drugs

When evaluating the design of pre-clinical studies in the field of traumatic brain injury, we found substantial differences compared to phase III clinical trials, which in part may explain the difficulties in translating promising experimental drugs into approved treatments. By using network analysis, we also found cases where a large proportion of the studies evaluating a pre-clinical treatment was performed by inter-related researchers, which is potentially problematic. Subjecting all pre-clinical trials to the rigor of a phase III clinical trial is, however, likely not practically achievable. Instead, we repeat the call for a distinction to be made between exploratory and confirmatory pre-clinical studies.

Gene Expression Profiling for Discovery of Novel Targets in Human Traumatic Brain Injury

2010 ◽  
Vol 13 (2) ◽  
pp. 140-153 ◽  
Author(s):  
Taura L. Barr ◽  
Sheila Alexander ◽  
Yvette Conley
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Clinical Trials ◽  
Brain Injury ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Treatment Strategies ◽  
Biological Pathways ◽  
Human Response ◽  
Novel Targets

Several clinical trials have failed to demonstrate a significant effect on outcome following human traumatic brain injury (TBI) despite promising results obtained in preclinical animal studies. These failures may be due in part to a misinterpretation of the findings obtained in preclinical animal models of TBI, a misunderstanding of the complexity of the human response to TBI, limited knowledge about the biological pathways that interact to contribute to good and bad outcomes after brain injury, and the effects of genomic variability and environment on individual recovery. Recent publications suggest that data obtained from gene expression profiling studies of complex neurological diseases such as stroke, multiple sclerosis (MS), Alzheimer’s and Parkinson’s may contribute to a more informed understanding of what affects outcome following TBI. These data may help to bridge the gap between successful preclinical studies and negative clinical trials in humans to reveal novel targets for therapy. Gene expression profiling has the capability to identify biomarkers associated with response to TBI, elucidate complex genetic interactions that may play a role in outcome following TBI, and reveal biological pathways related to brain health. This review highlights the current state of the literature on gene expression profiling for neurological disease and discusses its ability to aid in unraveling the variable human response to TBI and the potential for it to offer treatment strategies in an area where we currently have limited therapeutic options primarily based on supportive care.

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