Ignite Creation Date:
2024-05-06 @ 1:21 PM
Last Modification Date:
2024-10-26 @ 1:13 PM
Study NCT ID:
NCT04007328
Status:
RECRUITING
Last Update Posted:
2019-07-05
First Post:
2019-04-23
Brief Title:
Sphingosine-1-phosphate and Pneumonia
Sponsor:
Taipei Medical University WanFang Hospital
Organization:
Taipei Medical University WanFang Hospital
Study Overview
Official Title:
To Assess the Role of Sphingosine-1-phosphate in the Pathobiology of Pneumonia Generate a New Strategy for Treatment of Severe Community-acquired Pneumonia
Status:
RECRUITING
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SOPN
Brief Summary:
Pneumonia is a major infectious cause of death worldwide and imposes a considerable burden on healthcare resources Sphingosine-1-phosphate S1P is a bioactive sphingolipid and involved in many physiological processes including immune responses and endothelial barrier integrity In term of endothelial barrier integrity S1P plays a crucial role in protecting lungs from pulmonary leak and lung injury Because of the involvement in lung injury S1P could be the potential biomarker of pneumonia Recently our pilot study suggested that patients with CAP have significantly higher plasma S1P levels than healthy individuals Interestingly our observational study also showed significantly elevated S1P level in the patients who were treated with methylprednisolone during the hospitalization Based on the above evidence we hypothesize that S1P plays an important role in the pathobiology of pneumonia Moreover S1P is not only a useful biomarker for diagnosis of CAP but also can be an indicator for using corticosteroids adjuvant therapy
Detailed Description:
Lower respiratory tract infections are the most frequent infectious cause of death worldwide1 and impose a considerable burden on healthcare resources Sphingosine-1-phosphate S1P is a bioactive sphingolipid and has both extracellular and intracellular effects in mammalian cells2-5 S1P is involved in many physiological processes including immune responses and endothelial barrier integrity6-9 In the context of endothelial barrier integrity S1P plays a crucial role in protecting the lungs from the pulmonary leak and lung injury 10-13 Previous research suggests that at low concentrations S1P signaling through S1PR1 is crucial for enhancing endothelial barrier function 1314 The S1P induces actin polymerization and results in the spreading of endothelial cells which fill the intercellular gaps Also the S1P signaling can stabilize the endothelial cell-cell junctions such as adherens junction and tight junction 15-17 Both actin-dependent outward spreading of endothelial cells and cell junction stabilization enhance the endothelial barrier function However S1P at higher concentration 5 µM causes endothelial barrier disruption through binding of S1PR213 Thus exact maintenance of physiologic S1P concentrations and homeostasis of S1PRs and S1P synthesis and degradation seem to be crucial for the preservation of lung endothelial barrier integrity particularly in inflammatory lung diseases
Because of the involvement in lung injury and endothelial barrier function S1P may be a potential biomarker of pneumonia Moreover a recent study proposed that targeting the S1PS1P receptor 2-signaling pathway in the lung may provide a novel therapeutic perspective in pneumonia for the prevention of acute lung injury 18 Recently our pilot study suggests that the patients with CAP N 137 have significantly higher plasma S1P levels than controls N 78 Further the S1P levels but not CRP were found to be inversely correlated with PSI score CURB-65 score and hospital length of stay LOS in patients with CAP Our initial findings suggest that plasma S1P is a potential biomarker for predicting prognosis in CAP
Although corticosteroids adjuvant therapy for CAP is still controversial a recent meta-analysis study showed that corticosteroids adjuvant therapy in patients with the severe CAP could reduce the rate of in-hospital mortality and reduce the length of hospital stay19 Recently the long-standing dogma of cytokine repression by the glucocorticoid was challenged Vettorazzi et al proposed a new mechanism of glucocorticoid action They suggested that increased circulating sphingosine 1-phosphate levels resulting from the induction of sphingosine kinase 1 SphK1 by glucocorticoids were essential for the inhibition of pulmonary inflammation20 Interestingly our observational study also showed significantly elevated S1P levels in patients who were treated with methylprednisolone during hospitalization
Several studies have suggested that S1P can enhance pulmonary endothelial cell barrier function suggesting that higher S1P levels could be potentially beneficial Hence the patients who are unable to produce sufficient S1P might have a poor prognosis However in most of the studies CAP was not considered as a disease model and those results were based on cell lines and mouse models Therefore further clinical studies focusing on the role of S1P in the pathophysiology of pneumonia is needed
Because of the involvement in lung injury and endothelial barrier function S1P may be a potential biomarker of pneumonia Moreover a recent study proposed that targeting the S1PS1P receptor 2-signaling pathway in the lung may provide a novel therapeutic perspective in pneumonia for the prevention of acute lung injury 18 Recently our pilot study suggests that the patients with CAP N 137 have significantly higher plasma S1P levels than controls N 78 Further the S1P levels but not CRP were found to be inversely correlated with PSI score CURB-65 score and hospital length of stay LOS in patients with CAP Our initial findings suggest that plasma S1P is a potential biomarker for predicting prognosis in CAP
Although corticosteroids adjuvant therapy for CAP is still controversial a recent meta-analysis study showed that corticosteroids adjuvant therapy in patients with the severe CAP could reduce the rate of in-hospital mortality and reduce the length of hospital stay19 Recently the long-standing dogma of cytokine repression by the glucocorticoid was challenged Vettorazzi et al proposed a new mechanism of glucocorticoid action They suggested that increased circulating sphingosine 1-phosphate levels resulting from the induction of sphingosine kinase 1 SphK1 by glucocorticoids were essential for the inhibition of pulmonary inflammation20 Interestingly our observational study also showed significantly elevated S1P levels in patients who were treated with methylprednisolone during hospitalization
Several studies have suggested that S1P can enhance pulmonary endothelial cell barrier function suggesting that higher S1P levels could be potentially beneficial Hence the patients who are unable to produce sufficient S1P might have a poor prognosis However in most of the studies CAP was not considered as a disease model and those results were based on cell lines and mouse models Therefore further clinical studies focusing on the role of S1P in the pathophysiology of pneumonia is needed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None