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LIPId Profile Changes in Inflammatory Conditions Induced by SARS-CORoronavirus-2 (LIPICOR)

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ClinicalTrials.gov Identifier: NCT05113836
Recruitment Status : Recruiting
First Posted : November 9, 2021
Last Update Posted : November 9, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

In late 2019, a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of COVID-19 (COronaVIrus Disease-2019) in Hubei Province, China. COVID-19 has become a pandemic with approximately 4.1 million confirmed cases as of May 2020 resulting in 280,000 deaths worldwide. Between 5 and 20% of patients hospitalized with SARS-CoV-2 infection are admitted to the ICU with a mortality ranging from 25 to 60% depending on the series. At present, there is no effective targeted therapy against this viral infection.

High-density lipoproteins (HDL) are nanoparticles made up of apolipoproteins, mainly apoA1, associated with phospholipids whose main function is the reverse transport of cholesterol from peripheral tissues to the liver. This property gives HDL a major cardiovascular protective effect. In addition to this effect, studies have highlighted a number of properties such as anti-inflammatory, anti-apoptotic, anti-thrombotic and anti-oxidant effects of these particles. Furthermore, it has been shown that HDL is able to bind and neutralize bacterial lipopolysaccharides (LPS), promoting their elimination.

During bacterial sepsis, a rapid decrease in plasma HDL cholesterol (HDL-C) concentration has been demonstrated, but also an inverse correlation between mortality and HDL-C concentration. In addition to the quantitative decrease in HDL during sepsis, dysfunctions of these particles have been described, such as major differences in size, or a notable alteration in protein composition with, in particular, more pro-inflammatory proteins. In this context of both quantitative and qualitative alteration of HDL, authors have tested the efficacy of injection of either reconstituted HDL (apoA1 + phosphatidylcholines) or peptides structurally similar to ApoA1 in animal models of sepsis and have demonstrated a protective effect on morbidity and mortality, with in particular a decrease in the inflammatory state induced by sepsis.

Low-density lipoproteins (LDL) can also neutralize LPS and observational studies have shown a decrease in the concentration of LDL cholesterol (LDL-C) during sepsis. The authors also showed that low LDL-C was associated with a poor prognosis in patients with sepsis.

During COVID-19-induced sepsis, a few studies have demonstrated a decrease in lipoprotein (HDL and LDL) concentration. More specifically, some authors have found an association between low lipoprotein concentrations and increased disease severity. To the best of the knowledge of the investigators, no study has specifically investigated particulate dysfunction of lipoproteins and in particular HDL during severe COVID-19 infections. On the other hand, as it has been described that lipoproteins and particularly HDL can bind bacterial components (LPS or LTA) favoring their clearance, it can be envisaged that these particles can also bind SARS-CoV-2 components, and this, in a more or less strong way depending on the virus strain.

The preliminary results of the investigators show that in sepsis, serum amyloid A (SAA) protein tends to replace apolipoprotein A1, making HDL dysfunctional. In addition, paraoxonase-1, an antioxidant enzyme mainly carried by HDL, is almost absent or degraded in septic patients. The SAA/PON-1 ratio could allow to assess the severity of COVID-19 damage and to reinforce a possible therapeutic strategy based on the supplementation of severe patients with apolipoprotein A1 and PON-1 rich HDL nanoparticles.

Main objective: To evaluate the functionality of HDL as a prognostic marker of mortality in COVID-19 patients in ICU. To do so, a quantification of the SAA/PON-1 ratio at plasma level and on isolated lipoproteins will be performed by ELISA.


Condition or disease Intervention/treatment
SARS-CoV2 Infection Biological: Deep nasopharyngeal swab Biological: Blood sample at D1, D3 and D7

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Study Type : Observational
Estimated Enrollment : 135 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: LIPId Profile Changes in Inflammatory Conditions Induced by SARS-CORoronavirus-2 : LIPICOR Study
Actual Study Start Date : December 19, 2020
Estimated Primary Completion Date : January 5, 2022
Estimated Study Completion Date : July 1, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Any patient hospitalised in intensive care for a COVID-19 infection.
Any patient hospitalised in intensive care for a COVID-19 infection. The health emergency of this pandemic and the potential therapeutic action of HDL particles justify the choice of this population for study.
Biological: Deep nasopharyngeal swab
On admission in ICU, a deep nasopharyngeal swab will be performed (15mL).

Biological: Blood sample at D1, D3 and D7

Specific samples for research and lipid analysis will be performed at D1, D3 and D7:

Assessments will be carried out on the same blood tube as the blood ionogram carried out as part of the usual management.

This means a 5 ml tube of blood on EDTA medium will be taken at the same time as the blood ionogram for the treatment at D1, D3 and D7 (15mL in total).





Primary Outcome Measures :
  1. Change of concentration of Serum Amyloid A (SAA, inflammation protein) and paroxonase-1 (PON-1, antioxidant enzyme) in plasma and lipoproteins. [ Time Frame: Day 1 and Day 7. ]
    The primary endpoint will be the change of concentration of Serum Amyloid A (SAA, inflammation protein) and paroxonase-1 (PON-1, antioxidant enzyme) in plasma and lipoproteins. SAA and PON-1 will be quantified by ELISA directly in plasma and after isolating by ultracentrifugation lipoproteins (HDL and LDL) from Day 1 and Day 7.


Secondary Outcome Measures :
  1. Assessment of structural dysfunctions by proteomic approaches to lipoproteins during severe COVID-19 infections. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Assessment of structural dysfunctions by proteomic approaches to lipoproteins during severe COVID-19 infections.

  2. Quantification of plasma HDL-C, LDL-C and triglyceride concentrations over time in patients hospitalized in ICU for severe COVID-19 infection. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Quantification of plasma HDL-C, LDL-C and triglyceride concentrations over time in

  3. Study of HDL and LDL particle size profiles using the Lipo-print® technique. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Study of HDL and LDL particle size profiles using the Lipo-print® technique.

  4. Comparison of pro- and anti-inflammatory cytokines levels, such as IL-1 beta, IL-6, TNF-alpha, IL-10 or IL-18, in patients according to their particle dysfunction data. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Comparison of pro- and anti-inflammatory cytokines levels, such as IL-1 beta, IL-6, TNF-alpha, IL-10 or IL-18, in patients according to their particle dysfunction data.

  5. Comparison of particle dysfunction data to markers of endothelial dysfunction. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Comparison of particle dysfunction data to markers of endothelial dysfunction.

  6. Comparison of lipid profiles to the genotype of COVID-19 strains. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Comparison of lipid profiles to the genotype of COVID-19 strains.

  7. Search for binding of viral proteins to lipoproteins. [ Time Frame: Day 1, Day 3 and Day 7 ]
    Search for binding of viral proteins to lipoproteins.


Biospecimen Retention:   Samples Without DNA

On admission to the intensive care unit, a deep nasopharyngeal swab will be performed.

A 5 ml tube of blood on EDTA medium will be taken at the same time as the blood ionogram for the treatment at D1, D3 and D7.

During the research, the collection will be kept in the Biochemistry Laboratory of the Bichat Claude Bernard Hospital for a period of 2 years.

At the end of the research, the samples will be kept and the aliquots necessary for the lipoprotein characterisation + genotyping experiments will be transferred to the Natinal Institute of Medical Reasearch U1188 laboratory.

At the end of the research, the samples may be used for further analyses not foreseen in the protocol which may prove interesting in the context of the pathology according to the evolution of scientific knowledge, provided that the patient is not opposed to this, after having been informed, as indicated in the information/consent form.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Any patient hospitalised in intensive care for a COVID-19 infection. The health emergency of this pandemic and the potential therapeutic action of HDL particles justify the choice of this population for study.
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Patient hospitalized in surgical intensive care unit for COVID-19 infection.

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • CHILD B or C cirrhotic patients
  • Moribund patients with an estimated life expectancy of less than 48 hours on admission to the ICU
  • Subject protected by law under guardianship or curatorship
  • No affiliation to a social security system
  • Absence of signed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05113836


Contacts
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Contact: Sebastien TANAKA, MD, PhD 01 40 25 79 10 sebastien.tanaka@aphp.fr

Locations
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France
Hôpital Bichat Recruiting
Paris, France, 75018
Contact: Sebastien TANAKA, MD, PhD    01 40 25 79 10    sebastien.tanaka@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Sebastien TANAKA, MD, PhD Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT05113836    
Other Study ID Numbers: APHP20128
2020-A02638-3 ( Registry Identifier: ID-RCB )
First Posted: November 9, 2021    Key Record Dates
Last Update Posted: November 9, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Infecious disease
Sars-CoV2
COVID-19
LDL
HDL
SAA
PON-1
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases