Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00506454
Status:
COMPLETED
Last Update Posted:
2011-09-20
First Post:
2007-07-23
Brief Title:
Lipid Infusion in Dialysis Patients With Endotoxemia
Sponsor:
Sepsicure
Organization:
Sepsicure
Study Overview
Official Title:
A Phase II Double-Blind Placebo-Controlled Randomized Study of the Effects of a Lipid Emulsion Lipidose on Endotoxin Levels in Patients on Chronic Hemodialysis
Status:
COMPLETED
Status Verified Date:
2011-09
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:
LIPIDOSE
Brief Summary:
The purpose of this study is to determine whether a phospholipid emulsion is effective in the treatment of chronic endotoxemia in hemodialysis patients
Detailed Description:
Over 70 of dialysis patients suffer chronically from severe fatigue and tiredness A possible inciting factor may be high levels of circulating endotoxin which is well-established as a potent stimulator of inflammatory cytokine release
The source of increased endotoxin in dialysis patients remains unclear with the most popular hypotheses including back-diffusion of bacterial products from nonsterile dialysate and translocation of bacterial products across what in most dialysis patients is an edematous gut wall This endotoxin does not appear to be associated with the dialysis procedure itself and indeed appears to be cleared with some efficiency by the procedure However by the next dialysis treatment endotoxin levels rise rapidly to levels that are in some cases significantly higher than even those measured via EAA in patients suffering from septic shock Although the mechanisms by which dialysis patients tolerate these high endotoxin levels without hemodynamic collapse are not understood high levels have been shown by The Rogosin Institute to significantly correlate with patient fatigue
Given the potent ability of endotoxin to induce expression of inflammatory cytokines which in turn are likely responsible for the debilitating symptoms of fatigue and malaise that afflict the majority of the dialysis population it is logical that binding and inactivation of endotoxin may lead to improved clinical outcomes Unfortunately there are no products currently approved for this purpose in dialysis patients
One approach to this problem may be to augment the endogenous systems for endotoxin inactivation For example it has been suggested that the various serum lipoprotein fractions may in fact be a physiologic sink for endotoxin and other toxins via binding with surface phospholipids Therefore dialysis patients who as a population are characterized with hypocholesterolemia and hypolipoproteinemia are particularly at risk for the deleterious effects of endotoxemia
This has led to the development of LIPIDOSE a protein-free phospholipid emulsion The proposed mechanism of action of this compound is via remodeling of the infused phospholipids into lipoproteins thereby increasing lipoprotein and phospholipid content and facilitating greater endotoxin binding and neutralization LIPIDOSE has undergone extensive testing in both animals and humans and has been found to significantly increase serum phospholipid and lipoprotein concentrations improve survival in a lethal animal model of septic peritonitis and mitigate the symptoms of endotoxemia in healthy volunteers
The source of increased endotoxin in dialysis patients remains unclear with the most popular hypotheses including back-diffusion of bacterial products from nonsterile dialysate and translocation of bacterial products across what in most dialysis patients is an edematous gut wall This endotoxin does not appear to be associated with the dialysis procedure itself and indeed appears to be cleared with some efficiency by the procedure However by the next dialysis treatment endotoxin levels rise rapidly to levels that are in some cases significantly higher than even those measured via EAA in patients suffering from septic shock Although the mechanisms by which dialysis patients tolerate these high endotoxin levels without hemodynamic collapse are not understood high levels have been shown by The Rogosin Institute to significantly correlate with patient fatigue
Given the potent ability of endotoxin to induce expression of inflammatory cytokines which in turn are likely responsible for the debilitating symptoms of fatigue and malaise that afflict the majority of the dialysis population it is logical that binding and inactivation of endotoxin may lead to improved clinical outcomes Unfortunately there are no products currently approved for this purpose in dialysis patients
One approach to this problem may be to augment the endogenous systems for endotoxin inactivation For example it has been suggested that the various serum lipoprotein fractions may in fact be a physiologic sink for endotoxin and other toxins via binding with surface phospholipids Therefore dialysis patients who as a population are characterized with hypocholesterolemia and hypolipoproteinemia are particularly at risk for the deleterious effects of endotoxemia
This has led to the development of LIPIDOSE a protein-free phospholipid emulsion The proposed mechanism of action of this compound is via remodeling of the infused phospholipids into lipoproteins thereby increasing lipoprotein and phospholipid content and facilitating greater endotoxin binding and neutralization LIPIDOSE has undergone extensive testing in both animals and humans and has been found to significantly increase serum phospholipid and lipoprotein concentrations improve survival in a lethal animal model of septic peritonitis and mitigate the symptoms of endotoxemia in healthy volunteers
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