- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03392701
Possible Links Between Inflammation and Lipid Metabolism
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Linz, Austria, 4021
- Barmherzige Brüder Linz - Innere Medizin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men aged 18 to 40 years
- Written informed consent
- No disease history
- non-smoker
- BNP level within the normal range
- Normal renal function (serum creatinine of 1.3 mg/dL and/or creatinine clearance greater than 80ml/min)
Exclusion Criteria:
- Systolic blood pressure < 90 mmHg
- Subjects on any medication
- History of anaphylaxis
- Probands who suffer from infectious disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
NaCl
|
infusion of LPS 2 ng/kg over 5 minutes
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Experimental: LPS infusion
infusion of LPS 2 ng/kg over 5 minutes
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infusion of LPS 2 ng/kg over 5 minutes
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
lipid kinetics
Time Frame: 48 hours
|
levels of lipid parameters including LDL, HDL, lipoprotein(a), apolipoprotein A1 and apoB will be measured at multiple timepoints (t0, t15, t30, t60, t120, t180, t360, 24h and 48h) in order to evaluate the detaile kinetics of lipid parameters in inflammatory condidtions
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48 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Matthias Heinzl, MD, Barmherzige Brüder Linz
Publications and helpful links
General Publications
- Heinzl MW, Resl M, Klammer C, Fellinger P, Schinagl L, Obendorf F, Feldbauer R, Pohlhammer J, Wagner T, Egger M, Dieplinger B, Clodi M. SUBCLINICAL KIDNEY INJURY IS CAUSED BY A MODERATE SINGLE INFLAMMATORY EVENT. Shock. 2022 Jul 1;58(1):14-19. doi: 10.1097/SHK.0000000000001942. Epub 2022 Jul 19.
- Millischer V, Heinzl M, Faka A, Resl M, Trepci A, Klammer C, Egger M, Dieplinger B, Clodi M, Schwieler L. Intravenous administration of LPS activates the kynurenine pathway in healthy male human subjects: a prospective placebo-controlled cross-over trial. J Neuroinflammation. 2021 Jul 17;18(1):158. doi: 10.1186/s12974-021-02196-x.
- Heinzl MW, Resl M, Klammer C, Egger M, Dieplinger B, Clodi M. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Not Induced in Artificial Human Inflammation and Is Not Correlated with Inflammatory Response. Infect Immun. 2020 Feb 20;88(3):e00842-19. doi: 10.1128/IAI.00842-19. Print 2020 Feb 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LPS lipid metabolism
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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