Clinical trial NCT00506454
Conditions: Fatigue End Stage Renal Disease (ESRD)
Keywords: Fatigue Hemodialysis Endotoxemia Phospholipid Emulsion
Sponsor: Sepsicure
Start date: 2007-08-01; Completion date: 2008-02-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Dosage of 1.5 mL/kg of Lipidose over a 2-hour period. arm 2: Dosage of 1.5 mL/kg of Placebo over a 2-hour period.
Interventions: intervention 1: Lipidose intervention 2: Placebo
Intervention descriptions: intervention 1: Over the course of 2 weeks, immediately following subject's three (Monday/Wednesday/Friday (M/W/F)) normal dialysis treatments, based on subject's current weight, subject will receive 1.5 mL/kg of Lipidose over a 2-hour period. intervention 2: Over the course of 2 weeks, immediately following subject's three (M/W/F) normal dialysis treatments, based on subject's current weight, subject will receive 1.5 mL/kg of placebo over a 2-hour period.

Protocol documents: