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NCT Number: NCT06657781

Study and Role of Inflammasome in Platelet Activation During Bacterial And/or Viral Sepsis

: Sepsis, now defined as life-threatening organ dysfunction due to a dysregulated host response to infection, is an important global health problem representing about a fifth of all global deaths. It can be associated, in some cases, with multiple organ failure and cytokine storm. The main objective of this study is to estimate and to compare the activation rate of the Nucleotide-binding domain Leucine Rich repeat containing Protein 3 (NLRP3) inflammasome in platelets between five groups of patients suffering from bacterial and/or viral sepsis, with different severity levels according to Sequential Organ Failure Assessment (SOFA) score to precise the platelets' implication in this cytokine storm.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

Patients with bacterial or vial sepsis have been shown to exhibit very high levels of pro-inflammatory cytokines (IL1, IL6, IFN, IP10 and MCP1) that may activate the T-helper-1 lymphocytic response (Th1). These cytokines can be produced by several cell types, including blood platelets. IL1 is an important pro-inflammatory cytokine whose expression is increased in various pro-inflammatory contexts, including dengue infection. It induces an increase in endothelial permeability and a pro-thrombotic state, as described in patients infected with COVID-19. It is synthesized as a protein precursor that is cleaved by the NLRP3 (Nucleotide-binding domain Leucine repeat Rich containing Protein 3). Close associations between the deregulation of inflammasome activity and hereditary or acquired diseases suggest an important role of NLRP3 inflammasome in regulating immune responses. The activation of the NLRP3 inflammasome increases caspase 1 activity and induces the production of bioactive IL1 as well as other pro-inflammatory cytokines such as IL18. The major role of NLRP3 platelet inflammasome in the "cytokine storm" has been highlighted in the case of Dengue virus infection. We hypothesize that blood platelets may play an important role in the inflammatory response observed during sepsis through the activation of NLRP3 inflammasome, particularly during its exacerbation.

  • Five groups of patients will be constituted: patients with leptospirosis, patients with bacterial infections including in-hospital-acquired-infections, patients with viral infection, patients non infected (control group), patients with viral infection SARS-COv2 +.
  • Only one blood collection will be realized

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • For all groups: patients older than 18 years at inclusion and acceptation of participation by the patient, his relative or his legal representative (depending on the situation)
  • For groups 1, 2, 3 and 5: Patient with a confirmed sepsis (microbiological confirmation)
  • For group 4 : Patient non infected

Exclusion criteria

  • Refusal of participation by the patient, his relative or his legal representative (depending on the situation)
  • Patients subject to a safeguard measure of justice
  • Patients younger than 18 years at inclusion

Treatment and study plan

Primary outcomes

  1. Nucleotide-binding domain Leucine Rich repeat containing Protein 3 activation

    Time frame: Baseline

    The primary outcome will be the evaluation of platelets' NLRP3 activation in septic patients according to the severity of the disease

Secondary outcomes

  1. Confocal Microscopy

    Time frame: Baseline

    We aim to confirm the colocalization of NRLP3/ASC in inflammasome activation by confocal microscopy

Study contacts

Contact information is provided by the study sponsor or research team.

Frédéric MARTINO, Doctor

CONTACT

[email protected]

+590 590 89 10 10

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de la Guadeloupe

Other

Registry information

Acronym: PLAQSEPSIS

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Oct 24, 2024
Registry last updated
Oct 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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