Ignite Creation Date:
2024-05-05 @ 12:07 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00248638
Status:
COMPLETED
Last Update Posted:
2018-01-23
First Post:
2005-11-03
Brief Title:
Efficacy and Mechanisms of GLN Dipeptide in the SICU
Sponsor:
Emory University
Organization:
Emory University
Study Overview
Official Title:
Phase III Study on the Efficacy of Glutamine Dipeptide-Supplemented Parenteral Nutrition in Surgical ICU Patients
Status:
COMPLETED
Status Verified Date:
2018-01
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:
GLND
Brief Summary:
Relative glutamine GLN deficiency may contribute to morbidity and mortality in surgical intensive care unit SICU patients During critical illness GLN utilization by the immune system gut mucosa and other tissues exceeds endogenous production and plasma GLN concentrations decrease which may contribute to cellular dysfunction and increase nosocomial infection risk and mortality Conventional GLN-free parenteral nutrition PN has a limited impact on SICU outcomes and does not repair the GLN deficit Recent pilot data show that GLN dipeptide-supplemented PN decreases nosocomial infections and improves clinical outcomes in SICU patients The process of benefit is poorly understood but animal and human data suggest that GLN treatment correlates with a up-regulation of cytoprotective molecules in blood and tissues eg GSH specific heat shock proteins HSPs and GLN and b improved epithelial barrier defenses and immune cell number and function Properties of L-GLN limit provision in solution but the GLN dipeptide alanyl-GLN AG confers stability and solubility in PN AG-PN Investigators propose a multicenter double-blind randomized controlled phase III trial based on our pilot data to test the hypothesis that AG-PN improves clinical outcomes in SICU patients requiring PN after cardiac vascular or colonic operations Subjects will receive either standard GLN-free PN or isocaloric isonitrogenous AG-PN until enteral feeds are established Specific Aim 1 is to determine whether AG-PN decreases hospital mortality nosocomial infection and other important indices of morbidity Specific Aim 2 is to obtain novel mechanistically relevant observational data in the Aim 1 subjects on whether AG-PN a increases serial blood levels of GSH HSP-70 and -27 and GLN b decreases the presence in serum of the bacterial products flagellin and LPS and the adaptive immune response to these mediators and c improves key indices of innateadaptive immunity This study is designed to delineate the clinical benefit of a major new nutrition support strategy in high-risk SICU patients
Detailed Description:
Overview Relative deficiency of glutamine GLN appears to contribute to morbidity and mortality in surgical intensive care unit SICU patients but conventional nutrition support does not repair this deficit GLN requirements increase during critical illness when utilization by the immune system gut mucosa and other tissues exceeds endogenous production GLN depletion under these conditions may contribute to hospital morbidity and mortality Conventional parenteral nutrition PN does not contain GLN and thus does not prevent GLN depletion in catabolic patients However a pilot study and other reports strongly suggest that GLN-supplemented PN improves metabolic and clinical outcomes in critically ill patients Underlying mechanisms for GLN action are poorly understood but may involve systemic upregulation of the cytoprotective molecules glutathione GSH specific heat shock proteins HSP and GLN itself improved gut barrier defenses and improved innate andor adaptive immune function Properties of L-GLN limit provision in PN but the dipeptide alanyl-glutamine AG confers stability and solubility in PN solutions The pilot study demonstrated a marked decrease in nosocomial infection improved indices of organ function and a possible decrease in hospital mortality in SICU patients receiving AG-supplemented PN AG-PN versus standard GLN-free PN STD-PN Investigators propose a multi-center double-blind controlled Phase III trial based on a pilot study that will determine the effect of parenteral GLN on important clinical outcomes in patients requiring SICU care and PN after cardiac vascular or colonic surgery Investigators also propose to obtain needed hypothesis-generating descriptive data from the Aim 1 study subjects to inform subsequent truly mechanistic studies of GLN action in animal and human models of surgical critical illness Study subjects will be randomized on an intent-to-treat basis to receive AG-PN or isonitrogenous isocaloric STD-PN until enteral feeding is established
Hypotheses
1 SICU patients receiving PN supplemented with GLN dipeptide AG-PN will demonstrate improved clinical outcomes compared to patients receiving STD-PN
2 Administration of AG-PN in the Aim 1 study subjects a increases serial blood levels of specific cytoprotective molecules and improves systemic redox status b is associated with decreased serum positivity for the bacterial products flagellin and lipopolysaccharide LPS and the adaptive immune response to these mediators and c improves key indices of innateadaptive immunity
Specific Aims
Aim 1 To perform a Phase III randomized controlled trial RCT to determine whether AG-PN decreases hospital mortality nosocomial infections and other indices of hospital morbidity versus STD-PN in SICU patients The study will test whether AG-PN decreases hospital mortality and the incidence of nosocomial infection primary endpoints in SICU patients after cardiac vascular or colonic surgery We will also determine whether AG-PN decreases total hospital infections bloodstream infections BSI infections due to Staphylococcus aureus or fungal species the number of days patients require mechanical ventilation the SICU and total hospital length of stay and the 6-month mortality rate secondary endpoints
Aim 2 To determine in the Aim 1 study subjects whether AG-PN a increases systemic blood concentrations of the cytoprotective molecules GSH HSP-70 HSP-27 and GLN and improves systemic GSH and cysteine redox status b is associated with decreased serum positivity for the bacterial products flagellin and LPS and titers of anti-flagellin and anti-LPS immunoglobulin M IgM immunoglobulin A IgA and immunoglobulin G IgG and c improves key indices of innateadaptive immune cell function
Hypotheses
1 SICU patients receiving PN supplemented with GLN dipeptide AG-PN will demonstrate improved clinical outcomes compared to patients receiving STD-PN
2 Administration of AG-PN in the Aim 1 study subjects a increases serial blood levels of specific cytoprotective molecules and improves systemic redox status b is associated with decreased serum positivity for the bacterial products flagellin and lipopolysaccharide LPS and the adaptive immune response to these mediators and c improves key indices of innateadaptive immunity
Specific Aims
Aim 1 To perform a Phase III randomized controlled trial RCT to determine whether AG-PN decreases hospital mortality nosocomial infections and other indices of hospital morbidity versus STD-PN in SICU patients The study will test whether AG-PN decreases hospital mortality and the incidence of nosocomial infection primary endpoints in SICU patients after cardiac vascular or colonic surgery We will also determine whether AG-PN decreases total hospital infections bloodstream infections BSI infections due to Staphylococcus aureus or fungal species the number of days patients require mechanical ventilation the SICU and total hospital length of stay and the 6-month mortality rate secondary endpoints
Aim 2 To determine in the Aim 1 study subjects whether AG-PN a increases systemic blood concentrations of the cytoprotective molecules GSH HSP-70 HSP-27 and GLN and improves systemic GSH and cysteine redox status b is associated with decreased serum positivity for the bacterial products flagellin and LPS and titers of anti-flagellin and anti-LPS immunoglobulin M IgM immunoglobulin A IgA and immunoglobulin G IgG and c improves key indices of innateadaptive immune cell function
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| DK69322 | OTHER | Other | httpsreporternihgovquickSearchU01DK069322 |
| U01DK069322 | NIH | None | None |