Ignite Creation Date:
2024-05-06 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 12:44 PM
Study NCT ID:
NCT03497962
Status:
COMPLETED
Last Update Posted:
2018-04-13
First Post:
2015-05-08
Brief Title:
P4 Peptide in Community Acquired Pneumonia
Sponsor:
Liverpool University Hospitals NHS Foundation Trust
Organization:
Liverpool University Hospitals NHS Foundation Trust
Study Overview
Official Title:
Using P4 Peptide to Augment ex Vivo Phagocyte Function in Patients With Severe Community Acquired Pneumonia CAP
Status:
COMPLETED
Status Verified Date:
2017-05
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:
P4
Brief Summary:
The investigators aim is to find out whether immune cells from patients with a severe chest infection will react ex vivo to a new immunomodulating peptide P4 as part of augmented passive immunotherapy
The investigators know that P4 treatment can successfully improve the efficiency of specialized immune cells responsible for killing bacteria The investigators also know that P4 treatment is effective in healthy human volunteers but wish to extend this observation to patients that have infection as immune cells may react differently in these patients If this study is successful the investigators hope to be moving closer to a new treatment against severe bacterial infections
The investigators plan to recruit patients admitted to the Intensive Care Unit ICU and healthy volunteers using carefully established inclusion and exclusions criteria with severe community acquired pneumonia CAP and obtain both blood and if clinically feasible a bronchoscopy BAL sample washing of lung tissue
The investigators know that P4 treatment can successfully improve the efficiency of specialized immune cells responsible for killing bacteria The investigators also know that P4 treatment is effective in healthy human volunteers but wish to extend this observation to patients that have infection as immune cells may react differently in these patients If this study is successful the investigators hope to be moving closer to a new treatment against severe bacterial infections
The investigators plan to recruit patients admitted to the Intensive Care Unit ICU and healthy volunteers using carefully established inclusion and exclusions criteria with severe community acquired pneumonia CAP and obtain both blood and if clinically feasible a bronchoscopy BAL sample washing of lung tissue
Detailed Description:
The investigators will examine the response to P4 peptide of alveolar macrophages from bronchoalveolar lavage BAL and neutrophils from peripheral blood collected from patients with severe pneumonia admitted to the ITU
The investigators expect to show improved phagocytosis oxidative burst cellular activation flow cytometry electron microscopy cytokine production transcriptomics and bacterial killing when P4 is used to stimulate immune cells and this may lead to a novel approach to the treatment of severe infections
The investigators will also examine the effect of P4 on alveolar macrophages and neutrophils from healthy volunteers in order to ensure comparability with previously published results and extend observations using Spneumoniae to other causes of severe pneumonia including Ecoli Salmonellae Mtuberculosis and Pseudomonas
Augmented passive immunotherapy API is a novel potential treatment strategy to combat fulminant bacterial infections It consists of two components
1 a peptide that enhances bacterial uptake and killing by phagocytes
2 exogenous antibody provided with intravenous immunoglobulin a licensed medicinal product which optimizes the phagocytosis Previous studies of API have included extensive murine studies of acute and chronic bacterial infection with several different organisms P4 has also been tested in aged mice and in mucosal administration
The investigators will recruit patients with severe community acquired pneumonia on ICU and healthy volunteers using carefully established inclusion and exclusions criteria
This research seeks to establish proof-of-concept for augmented passive immunotherapy in patients with severe pneumonia Patients with mild to moderate pneumonia often respond to antibiotic therapy but those with severe community-acquired pneumonia who require admission to Intensive Care have a hospital mortality of 494 despite antibiotics and optimal supportive care These patients represent 6 of all admissions to Intensive Care Units in the UK Strategies to improve clinical outcome for this group of patients are much needed and the investigators research cohort has been selected to represent this group The immunological characteristics of patients with overwhelming sepsis are likely to differ from patients with milder infection Immune cells taken from patients with milder forms of sepsis may not respond to in vitro stimulation in the same way as cells taken from severely septic patients and therefore should not be used to establish proof-of-concept for a therapy intended for critically ill patients on Intensive Care
The investigators expect to show improved phagocytosis oxidative burst cellular activation flow cytometry electron microscopy cytokine production transcriptomics and bacterial killing when P4 is used to stimulate immune cells and this may lead to a novel approach to the treatment of severe infections
The investigators will also examine the effect of P4 on alveolar macrophages and neutrophils from healthy volunteers in order to ensure comparability with previously published results and extend observations using Spneumoniae to other causes of severe pneumonia including Ecoli Salmonellae Mtuberculosis and Pseudomonas
Augmented passive immunotherapy API is a novel potential treatment strategy to combat fulminant bacterial infections It consists of two components
1 a peptide that enhances bacterial uptake and killing by phagocytes
2 exogenous antibody provided with intravenous immunoglobulin a licensed medicinal product which optimizes the phagocytosis Previous studies of API have included extensive murine studies of acute and chronic bacterial infection with several different organisms P4 has also been tested in aged mice and in mucosal administration
The investigators will recruit patients with severe community acquired pneumonia on ICU and healthy volunteers using carefully established inclusion and exclusions criteria
This research seeks to establish proof-of-concept for augmented passive immunotherapy in patients with severe pneumonia Patients with mild to moderate pneumonia often respond to antibiotic therapy but those with severe community-acquired pneumonia who require admission to Intensive Care have a hospital mortality of 494 despite antibiotics and optimal supportive care These patients represent 6 of all admissions to Intensive Care Units in the UK Strategies to improve clinical outcome for this group of patients are much needed and the investigators research cohort has been selected to represent this group The immunological characteristics of patients with overwhelming sepsis are likely to differ from patients with milder infection Immune cells taken from patients with milder forms of sepsis may not respond to in vitro stimulation in the same way as cells taken from severely septic patients and therefore should not be used to establish proof-of-concept for a therapy intended for critically ill patients on Intensive Care
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None