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Lipid Infusion in Dialysis Patients With Endotoxemia (LIPIDOSE)

Primary Purpose

Fatigue, End Stage Renal Disease (ESRD)

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Lipidose

Placebo

About this trial

This is an interventional treatment trial for Fatigue focused on measuring Fatigue, Hemodialysis, Endotoxemia, Phospholipid, Emulsion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

On hemodialysis for ≥ 3 months.
Provided written and dated informed consent.
Meets the following lab parameters on Screening labs:
- Serum albumin > 2.5 g/dL;
- Serum total cholesterol > 95 mg/dL;
- Serum High-Density Lipoprotein (HDL) > 20 mg/dL;
- Serum hemoglobin ≥ 11 g/dL;
- Serum transaminases < 2x the upper limit of normal.
Has had a dialysis adequacy level (KT/V) greater than 1.3 for 2 months prior to screening.
Has a vitality score of ≤ 16 at time of screening.

Exclusion Criteria:

Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment in this study.
Pregnant, breast-feeding or female of childbearing potential who does not agree to remain abstinent or to use an acceptable contraceptive regimen (oral contraceptive, double-barrier method, or abstention from sexual relations) during the study period.
Has any of the following laboratory abnormalities when screened:
- Serum haptoglobin below the lower limit of normal;
- Lactate dehydrogenase (LDH) > 300 U/L;
- Low-Density Lipoprotein (LDL) > 190 mg/dL;
- Fasting (8 hours, water only) triglyceride level > 300 mg/dL;
- Serum phospholipid level > 500 mg/dL.
Has an EAA level < 0.6 Endotoxin Activity (EA) at screening.
Has prolonged heart wave (QT) interval (as defined by corrected QT (QTc) > 460 msec in males and > 470 msec in females) on screening electrocardiogram (ECG).
Has a history of allergic reaction to eggs (or egg products), soybeans, Intralipid, or any component of "LIPIDOSE".
Has had a recent hospitalization (within the last 30 days) or has other acute illness.
Deemed not medically or psychiatrically stable for the study (in opinion of investigator or the subject's primary nephrologist).
Currently on any of the following medications: (a) medications known to cause QT prolongation; (b) parenteral nutrition supplements (e.g., Intralipid); (c)amphotericin; (d) liposomal amphotericin; (e) amphotericin B lipid complex; or (f) coumadin.
Has known preexisting systolic dysfunction (as defined by previous echocardiogram with ejection fraction (EF) < 35%).
Currently receiving one of the following prohibited concomitant medications; parenteral nutrition supplements containing lipid "emulsion" (e.g., Intralipid), amphotericin, liposomal amphotericin, or amphotericin B lipid complex.
Has a known active hemolytic disease; immune hemolytic anemias, hemoglobinopathies (sickle cell anemia and thalassemia major) or is known or believed to suffer from hereditary spherocytosis or S.E. Asian elliptocytosis.
Has a known bone marrow disorder of inadequate red cell production (e.g., aplastic anemia, myelodysplasia).
Has known current alcohol or drug abuse.

Sites / Locations

Rogosin Manhattan Dialysis Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Lipidose

Placebo

Arm Description

Dosage of 1.5 mL/kg of Lipidose over a 2-hour period.

Dosage of 1.5 mL/kg of Placebo over a 2-hour period.

Outcomes

Primary Outcome Measures

Reduction in Endotoxin Levels.

The number of participants whose post-hemodialysis endotoxin (as measured by Endotoxin Activity Assay (EAA)) was less than their pre-hemodialysis endotoxin.

Secondary Outcome Measures

Full Information

NCT ID

NCT00506454

First Posted

July 23, 2007

Last Updated

September 16, 2011

Sponsor

Sepsicure

Collaborators

The Rogosin Institute

1. Study Identification

Unique Protocol Identification Number

NCT00506454

Brief Title

Lipid Infusion in Dialysis Patients With Endotoxemia

Acronym

LIPIDOSE

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

February 2008 (Actual)

Study Completion Date

February 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sepsicure

Collaborators

The Rogosin Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fatigue, End Stage Renal Disease (ESRD)

Keywords

Fatigue, Hemodialysis, Endotoxemia, Phospholipid, Emulsion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lipidose

Arm Type

Active Comparator

Arm Description

Dosage of 1.5 mL/kg of Lipidose over a 2-hour period.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Dosage of 1.5 mL/kg of Placebo over a 2-hour period.

Intervention Type

Drug

Intervention Name(s)

Lipidose

Other Intervention Name(s)

GR270773

Intervention Description

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 Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Reduction in Endotoxin Levels.

Description

The number of participants whose post-hemodialysis endotoxin (as measured by Endotoxin Activity Assay (EAA)) was less than their pre-hemodialysis endotoxin.

Time Frame

Baseline and at 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: On hemodialysis for ≥ 3 months. Provided written and dated informed consent. Meets the following lab parameters on Screening labs: Serum albumin > 2.5 g/dL; Serum total cholesterol > 95 mg/dL; Serum High-Density Lipoprotein (HDL) > 20 mg/dL; Serum hemoglobin ≥ 11 g/dL; Serum transaminases < 2x the upper limit of normal. Has had a dialysis adequacy level (KT/V) greater than 1.3 for 2 months prior to screening. Has a vitality score of ≤ 16 at time of screening. Exclusion Criteria: Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment in this study. Pregnant, breast-feeding or female of childbearing potential who does not agree to remain abstinent or to use an acceptable contraceptive regimen (oral contraceptive, double-barrier method, or abstention from sexual relations) during the study period. Has any of the following laboratory abnormalities when screened: Serum haptoglobin below the lower limit of normal; Lactate dehydrogenase (LDH) > 300 U/L; Low-Density Lipoprotein (LDL) > 190 mg/dL; Fasting (8 hours, water only) triglyceride level > 300 mg/dL; Serum phospholipid level > 500 mg/dL. Has an EAA level < 0.6 Endotoxin Activity (EA) at screening. Has prolonged heart wave (QT) interval (as defined by corrected QT (QTc) > 460 msec in males and > 470 msec in females) on screening electrocardiogram (ECG). Has a history of allergic reaction to eggs (or egg products), soybeans, Intralipid, or any component of "LIPIDOSE". Has had a recent hospitalization (within the last 30 days) or has other acute illness. Deemed not medically or psychiatrically stable for the study (in opinion of investigator or the subject's primary nephrologist). Currently on any of the following medications: (a) medications known to cause QT prolongation; (b) parenteral nutrition supplements (e.g., Intralipid); (c)amphotericin; (d) liposomal amphotericin; (e) amphotericin B lipid complex; or (f) coumadin. Has known preexisting systolic dysfunction (as defined by previous echocardiogram with ejection fraction (EF) < 35%). Currently receiving one of the following prohibited concomitant medications; parenteral nutrition supplements containing lipid "emulsion" (e.g., Intralipid), amphotericin, liposomal amphotericin, or amphotericin B lipid complex. Has a known active hemolytic disease; immune hemolytic anemias, hemoglobinopathies (sickle cell anemia and thalassemia major) or is known or believed to suffer from hereditary spherocytosis or S.E. Asian elliptocytosis. Has a known bone marrow disorder of inadequate red cell production (e.g., aplastic anemia, myelodysplasia). Has known current alcohol or drug abuse.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roxana Bologa, MD

Organizational Affiliation

The Rogosin Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rogosin Manhattan Dialysis Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

12. IPD Sharing Statement

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Lipid Infusion in Dialysis Patients With Endotoxemia

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