FatiguePhase 2LIPIDOSENCT00506454
Lipid Infusion in Dialysis Patients With Endotoxemia
A Phase 2 study testing Lipidose in people with Fatigue and End Stage Renal Disease (ESRD), run by Sepsicure at 1 site in United States.
Trial summary
The purpose of this study is to determine whether a phospholipid emulsion is effective in the treatment of chronic endotoxemia in hemodialysis patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fatigue, End Stage Renal Disease (ESRD)
- What is being tested?
- Lipidose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Feb 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rogosin Manhattan Dialysis Center
New York, New York, 10021
About this study
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
The purpose of this study is to determine whether a phospholipid emulsion is effective in the treatment of chronic endotoxemia in hemodialysis patients.
Read the 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.
- Conditions
- Fatigue, End Stage Renal Disease (ESRD)
- Being tested
- Lipidose, Placebo
- Keywords
- Fatigue, Hemodialysis, Endotoxemia, Phospholipid, Emulsion
- Medical subject headings
- Fatigue, Kidney Failure, Chronic, Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LipidoseDrug
Also called GR270773
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Lipidose | Active comparator | Dosage of 1.5 mL/kg of Lipidose over a 2-hour period. Receives: Drug: Lipidose |
| Placebo | Placebo comparator | Dosage of 1.5 mL/kg of Placebo over a 2-hour period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2007 (estimated)
- Study startAug 2007
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FatigueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sepsicure
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Rogosin Institute
- Responsible party
- Sponsor
- Investigators
- Roxana Bologa, MD, Principal investigator, The Rogosin Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00506454
- Sponsor's protocol ID
- S201
- Acronym
- LIPIDOSE
- Status last verified
- Sep 2011
- First submitted
- 23 Jul 2007
- Last updated
- 20 Sep 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00506454
- Acronym / sponsor ID
- LIPIDOSE / S201
- Conditions
- Fatigue, End Stage Renal Disease (ESRD)
- Keywords
- Fatigue, Hemodialysis, Endotoxemia, Phospholipid, Emulsion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- SepsicureIndustry (pharma, biotech, devices)
- Collaborators
- The Rogosin Institute
- Study start
- Aug 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 25 Jul 2007 (estimated)
- Results
- Posted 15 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lipidose | Active comparator | Drug: LipidoseDosage of 1.5 mL/kg of Lipidose over a 2-hour period. |
| Placebo | Placebo comparator | Drug: PlaceboDosage of 1.5 mL/kg of Placebo over a 2-hour period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- On hemodialysis for ≥ 3 months.
- Provided written and dated informed consent.
- Meets the following lab parameters on Screening labs:
- 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.
Key exclusion criteria (19 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LipidoseAlso: GR270773Over 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. | Drug | Lipidose |
| PlaceboOver 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. | Drug | Placebo |
Primary outcome
Reduction in Endotoxin Levels.
Time frame: Baseline and at 4 weeks
The number of participants whose post-hemodialysis endotoxin (as measured by Endotoxin Activity Assay (EAA)) was less than their pre-hemodialysis endotoxin.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roxana Bologa, MD principal investigator
The Rogosin Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lipidose in people with Fatigue and End Stage Renal Disease (ESRD), run by Sepsicure at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in Endotoxin Levels. (time frame: Baseline and at 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2011.