Dataset Information

Clinical Trials of Immunomodulation in Ischemic Stroke.

ABSTRACT: Inflammatory mechanisms are currently considered as a prime target for stroke therapy. There is evidence from animal studies that immune signals and mediators can have both detrimental and beneficial effects in particular stages of the disease process. Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. Several clinical proof-of concept trials have investigated the efficacy of different immunomodulatory approaches in patients with stroke. Trials targeting the innate immune system have focused on reduction of microglial activation, inhibition of neutrophil migration, and interleukin-1 receptor blockade, suggesting that interleukin-1 receptor blockade may be a promising strategy. Studies aiming at halting T-cell migration have also been undertaken with controversial findings regarding prevention of infarct growth in neuroimaging studies. Consistently, recent proof-of-concept trials targeting lymphocytes with drugs such as natalizumab and fingolimod have yielded some promising results on clinical endpoints, but confirmation in larger trials is needed. At present, the understanding of the role of immune mechanisms in neurorepair and neurodegeneration is limited. Improving long-term brain function by mitigating prolonged neuroinflammation that was triggered by acute brain injury could be a strategy in addition to neuroprotection.

SUBMITTER: Veltkamp R

PROVIDER: S-EPMC5081130 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Clinical Trials of Immunomodulation in Ischemic Stroke.

Veltkamp Roland R Gill Dipender D

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20161001 4

Inflammatory mechanisms are currently considered as a prime target for stroke therapy. There is evidence from animal studies that immune signals and mediators can have both detrimental and beneficial effects in particular stages of the disease process. Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. Several clinical proof-of concept trials have investigated the efficacy of different immunomodulatory ...[more]

PMID: 27412685

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Project description:Despite improved treatment, a large portion of patients with acute ischemic stroke due to a large vessel occlusion have poor functional outcome. Further research exploring novel treatments and better patient selection has therefore been initiated. The feasibility of new treatments and optimized patient selection are commonly tested in extensive and expensive randomized clinical trials. in-silico trials, computer-based simulation of randomized clinical trials, have been proposed to aid clinical trials. In this white paper, we present our vision and approach to set up in-silico trials focusing on treatment and selection of patients with an acute ischemic stroke. The INSIST project (IN-Silico trials for treatment of acute Ischemic STroke, www.insist-h2020.eu) is a collaboration of multiple experts in computational science, cardiovascular biology, biophysics, biomedical engineering, epidemiology, radiology, and neurology. INSIST will generate virtual populations of acute ischemic stroke patients based on anonymized data from the recent stroke trials and registry, and build on the existing and emerging in-silico models for acute ischemic stroke, its treatment (thrombolysis and thrombectomy) and the resulting perfusion changes. These models will be used to design a platform for in-silico trials that will be validated with existing data and be used to provide a proof of concept of the potential efficacy of this emerging technology. The platform will be used for preliminary evaluation of the potential suitability and safety of medication, new thrombectomy device configurations and methods to select patient subpopulations for better treatment outcome. This could allow generating, exploring and refining relavant hypotheses on potential causal pathways (which may follow from the evidence obtained from clinical trials) and improving clinical trial design. Importantly, the findings of the in-silico trials will require validation under the controlled settings of randomized clinical trials.

Dataset Information

Clinical Trials of Immunomodulation in Ischemic Stroke.

Publications

Clinical Trials of Immunomodulation in Ischemic Stroke.

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