Clinical Trials Logo

Clinical Trial Summary

It has been recognized lately that sepsis and inflammation has an important impact on lipid metabolism and that the extent of hypocholesterolemia may even be a marker of severity of illness. However, the interplay between inflammation and the marked changes in lipid metabolism remain to be sufficiently understood. Importantly, the exact kinetics of lipid parameters in inflammatory conditions are yet to be explored. This study aims to investigate the interaction between inflammation and lipid metabolism using the human endotoxin model (LPS infusion) in ten healthy volunteers in a single blinded randomized placebo controlled cross-over design.


Clinical Trial Description

Sepsis is a severe clinical syndrome with still limited means of therapy and often poor prognosis. It has been recognized lately that sepsis and inflammation has an important impact on lipid metabolism and that the extent of hypocholesterolemia may even be a marker of severity of illness.

This study aims to investigate the interaction between inflammation and lipid metabolism and the possible role of various markers of lipid metabolism including apolipoprotein B, apoA1 and lipoprotein(A) using the human endotoxin model in ten healthy volunteers. In this model, volunteers are infused intravenously with bacterial lipopolysaccharide (LPS, 2 ng/kg over 5 minutes) to simulate human sepsis. Immediately after the infusion of LPS, proinflammatory cytokines and other mediators are elevated just as they are in common sepsis. This widely used model thus represents a reliable method for evaluating conditions during inflammation.

In this study, LPS will be administered to ten healthy male volunteers aged 18-40 years and plasma levels of lipid parameters including those described above will subsequently be measured repeatedly to evaluate the influence of LPS on lipid metabolism and detailed kinetics of lipid parameters.

This project is planned as a prospective, single blinded randomized, placebo controlled cross-over study. Participants must be free of disease history and previous anaphylactic events, must not be on any medication and will be screened for medical disorders including renal, hepatic and cardiovascular conditions, thrombophilia and infections in an initial medical examination. Each participant will be studied on two different study days with a washout period of at least 14 days, on which either LPS (National Reference Bacterial Endotoxin, lot EC-6, prepared from Escherichia coli 0113, USPC, Inc. Rockville, MD) and saline or saline alone as a placebo will be administered. LPS will be infused in a dosage of 2 ng/kg over a period of 5 minutes. Participants will be studied after an overnight fast and after 24 hours without smoking and without consumption of caffeine-containing beverages in order to ensure standard baseline conditions. During the study, subjects will rest in a supine position. Infusion and sampling will be done using two separate intravenous catheters.

Blood samples will be centrifuged, transferred into chilled tubes and placed on ice. Plasma will be frozen at -80°C until it will be assayed. Plasma and urine sodium, potassium, creatinine and glucose will be measured via routine laboratory techniques.

A case record form will be completed for each volunteer and data will subsequently be handled in an anonymous manner. Data will be analysed using repeated measures ANOVA.

In summary, this study aims to evaluate the interactions between sepsis and lipid metabolism using the human endotoxin model. Such knowledge could improve the understanding of the pathophysiology in sepsis and may lead to the development of novel therapeutic strategies. Insights on possible interactions between inflammation and lipid metabolism could also enlighten pathophysiological pathways in metabolic syndrome and type 2 diabetes mellitus causing chronic low-grade inflammation with potential impact on various medical fields. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03392701
Study type Interventional
Source Barmherzige Brüder Linz
Contact
Status Completed
Phase N/A
Start date December 20, 2017
Completion date September 30, 2018

See also
  Status Clinical Trial Phase
Active, not recruiting NCT05095324 - The Biomarker Prediction Model of Septic Risk in Infected Patients
Completed NCT02714595 - Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens Phase 3
Completed NCT03644030 - Phase Angle, Lean Body Mass Index and Tissue Edema and Immediate Outcome of Cardiac Surgery Patients
Completed NCT02867267 - The Efficacy and Safety of Ta1 for Sepsis Phase 3
Completed NCT04804306 - Sepsis Post Market Clinical Utility Simple Endpoint Study - HUMC
Recruiting NCT05578196 - Fecal Microbial Transplantation in Critically Ill Patients With Severe Infections. N/A
Terminated NCT04117568 - The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
Completed NCT03550794 - Thiamine as a Renal Protective Agent in Septic Shock Phase 2
Completed NCT04332861 - Evaluation of Infection in Obstructing Urolithiasis
Completed NCT04227652 - Control of Fever in Septic Patients N/A
Enrolling by invitation NCT05052203 - Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Recruiting NCT04005001 - Machine Learning Sepsis Alert Notification Using Clinical Data Phase 2
Completed NCT03258684 - Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis and Septic Shock N/A
Recruiting NCT05217836 - Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
Completed NCT05018546 - Safety and Efficacy of Different Irrigation System in Retrograde Intrarenal Surgery N/A
Completed NCT03295825 - Heparin Binding Protein in Early Sepsis Diagnosis N/A
Not yet recruiting NCT06045130 - PUFAs in Preterm Infants
Not yet recruiting NCT05361135 - 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia N/A
Not yet recruiting NCT05443854 - Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01) Phase 3