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Inflammasome Activation Via Circulating Metabolites

NCT03191175 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 55

Last updated 2018-09-28

No results posted yet for this study

Summary

The clinical challenges confronting patients with HIV has shifted over the past 10 years from acquired immunodeficiency syndrome to chronic diseases including atherosclerosis, neurocognitive disorders, and osteoporosis. Chronic low grade inflammation and monocyte activation have been consistently associated with comorbidities in HIV patients. Indeed, recent studies indicate that inflammatory mediators including IL-6, IL-1, sCD14 and s CD163 produced by monocytes, but not T-cell activation, predict Non-AIDS-related events in virologically suppressed HIV-infected persons treated with combined antiretroviral therapy (cART), highlighting the important role of monocyte activation in the occurrence of comorbidities in cART-treated HIV infected patients. Yet, the underlying molecular pathways of persistent monocyte activation in cART treated HIV-infected patients remains incompletely characterized. Our preliminary results: 1/ establish a link between the activation of the inflammasome, the increased of pyrimidine-derived metabolites and the cardiovascular risk in a cohort of elderly patients; 2/ show that treated HIV-patients are characterized by increased soluble IL-1b or IL-18 in their blood suggesting that the inflammasome pathway is activated.

Objectives: In this study we will characterize the molecular pathways underlying persistent monocyte activation in treated HIV patients, through the implication of the activation of the inflammasome machinery: 1. Characterization of NOD like Receptor (NLR) expression in monocytes for IL-1b and IL-18 secretion (inflammasome activation); 2. Characterization of circulating metabolites that active the inflammasome machinery; 3. Evaluation of the link between the activation of the inflammasome, the increased of circulating metabolites and the non-AIDS related comorbidities.

Conditions

  • Human Immunodeficiency Virus

Interventions

OTHER

blood sample

47ml blood (40 ml EDTA whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation and 7 ml for serum).

Sponsors & Collaborators

  • ANRS, Emerging Infectious Diseases

    collaborator OTHER_GOV

  • Sidaction

    collaborator OTHER

  • Centre National de la Recherche Scientifique, France

    collaborator OTHER

  • University Hospital, Bordeaux

    lead OTHER

Principal Investigators

  • Linda WITTKOP, MD, PhD · Université de Bordeaux - ISPED - Inserm 2129 - CHU de Bordeaux

  • Isabelle PELLEGRIN, MD, PhD · University Hospital, Bordeaux

  • Benjamin FAUSTIN, PhD · Centre National de la Recherche Scientifique, France

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2017-07-03
Primary Completion
2017-12-20
Completion
2017-12-20

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03191175 on ClinicalTrials.gov