scholarly journals Feasibility of progesterone treatment for ischaemic stroke

2015 ◽  
Vol 36 (3) ◽  
pp. 487-491 ◽  
Author(s):  
Claire L Gibson ◽  
Philip M Bath
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Injury ◽  
Ischaemic Stroke ◽  
Clinical Development ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Progesterone Treatment

Two multi-centre phase III clinical trials examining the protective potential of progesterone following traumatic brain injury have recently failed to demonstrate any improvement in outcome. Thus, it is timely to consider how this impacts on the translational potential of progesterone treatment for ischaemic stroke. A wealth of experimental evidence supports the neuroprotective properties of progesterone, and associated metabolites, following various types of central nervous system injury. In particular, for ischaemic stroke, studies have also begun to reveal possible mechanisms of such neuroprotection. However, the results in traumatic brain injury now question whether further clinical development of progesterone for ischaemic stroke is relevant.

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.

scholarly journals Aggregated n-of-1 trials of central nervous system stimulants versus placebo for paediatric traumatic brain injury – a pilot study

Trials ◽  
2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Catherine J Nikles ◽  
Lynne McKinlay ◽  
Geoffrey K Mitchell ◽  
Sue-Ann S Carmont ◽  
Hugh E Senior ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Pilot Study ◽  
Central Nervous System Stimulants

Central Nervous System Genomics

2011 ◽  
Vol 29 (1) ◽  
pp. 205-226 ◽  
Author(s):  
Matthew J. Gallek ◽  
Leslie Ritter
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Genomic Research ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
The Central Nervous System ◽  
Remarkable Progress ◽  
Made In

In the past 25 years, remarkable progress has been made in our understanding of genomics and its influence on central nervous system diseases. In this chapter, common diseases of the central nervous system will be reviewed along with the genomics associated with these diseases. The diseases/injuries that will be investigated include neurovascular disorders such as ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, and traumatic brain injury. This chapter will also explore Apolipoprotein E (APOE), a 299-aminoacid protein encoded by the APOE gene, and its associations with many of the previously named diseases. APOE was first tied to the risk of Alzheimer's disease and has since then been investigated in traumatic brain injury and hemorrhagic strokes. In addition, we will discuss the future of genomic research in central nervous system diseases.

scholarly journals Therapeutic Neutralization of the NLRP1 Inflammasome Reduces the Innate Immune Response and Improves Histopathology after Traumatic Brain Injury

2009 ◽  
Vol 29 (7) ◽  
pp. 1251-1261 ◽  
Author(s):  
Juan Pablo de Rivero Vaccari ◽  
George Lotocki ◽  
Ofelia F Alonso ◽  
Helen M Bramlett ◽  
W Dalton Dietrich ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Nlrp1 Inflammasome ◽  
Caspase 1 ◽  
Fluid Percussion Injury ◽  
Apoptosis Protein

Traumatic brain injury elicits acute inflammation that in turn exacerbates primary brain damage. A crucial part of innate immunity in the immune privileged central nervous system involves production of proinflammatory cytokines mediated by inflammasome signaling. Here, we show that the nucleotide-binding, leucine-rich repeat pyrin domain containing protein 1 (NLRP1) inflammasome consisting of NLRP1, caspase-1, caspase-11, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), the X-linked inhibitor of apoptosis protein, and pannexin 1 is expressed in neurons of the cerebral cortex. Moderate parasagittal fluid-percussion injury (FPI) induced processing of interleukin-1β, activation of caspase-1, cleavage of X-linked inhibitor of apoptosis protein, and promoted assembly of the NLRP1 inflammasome complex. Anti-ASC neutralizing antibodies administered immediately after fluid-percussion injury to injured rats reduced caspase-1 activation, X-linked inhibitor of apoptosis protein cleavage, and processing of interleukin-1β, resulting in a significant decrease in contusion volume. These studies show that the NLRP1 inflammasome constitutes an important component of the innate central nervous system inflammatory response after traumatic brain injury and may be a novel therapeutic target for reducing the damaging effects of posttraumatic brain inflammation.

scholarly journals A 20-Year Analysis of Clinical Trials Involving Proton Beam Therapy

2016 ◽  
Vol 3 (3) ◽  
pp. 398-406 ◽  
Author(s):  
Bismarck C. L. Odei ◽  
Dustin Boothe ◽  
Sameer R. Keole ◽  
Carlos E. Vargas ◽  
Robert L. Foote ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Proton Beam ◽  
Phase Ii ◽  
Proton Beam Therapy ◽  
Primary Treatment ◽  
Particle Therapy ◽  
Phase Iii ◽  
Phase Ii Trials

Purpose: Clinical trials (CTs) in proton beam therapy (PBT) are important for determining its benefits relative to other treatments. An analysis of PBT trials is, thus, warranted to understand the current state of PBT CTs and the factors affecting current and future trials. Materials and Methods: We queried the clinicaltrials.gov Website using the search terms: proton beam therapy, proton radiation, and protons. A total of 152 PBT CTs were identified. We used χ2 analysis and logistic regression to evaluate trial characteristics. Results: Most CTs were recruiting (n = 79; 52.0%), phase II (n = 95; 62.5%), open label (n = 134; 88.2%), single-group assignment (n = 84; 55.3%), and with primary treatment endpoints of safety and efficacy (n = 94; 61.8%). The primary treatment sites included gastrointestinal (n = 32; 21.1%), central nervous system (n = 31; 20.4%), lung (n = 21; 13.8%), prostate (n = 19; 12.5%), sarcoma (n = 15; 9.9%), and others (n = 24; 15.8%). Comparison studies between radiation modalities involved PBT and intensity-modulated photon therapy (n = 11; 7.2%), PBT and general photon therapy (n = 8; 5.3%), and PBT and carbon-ion therapy (n = 7; 4.6%). The PBT CTs underwent substantial growth after 2008 but now appear to be in decline. Nongovernmental institutions, comprising university centers, hospital systems, and research groups, have funded the greatest number of CTs (n= 106; 69.7%). The National Institutes of Health (NIH) were more likely to fund CTs involving the central nervous system ( P = 0.02). Trials involving NIH funding were more likely to result in successful trial completion ( P = 0.02). Conclusion: Among PBT CTs, most were phase II trials, with a very few being phase III CTs. Funding of PBT CTs originating from industry or the NIH is limited. Recently, there has been a declining trajectory of newly initiated PBT trials. It is not yet clear whether this represents a true trend or just a pause in CT implementation. Despite multiple impediments to PBT CTs, the particle therapy community continues to work toward evidence generation.

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