Inflammasome Activation Via Circulating Metabolites (InflammoVIH)

September 27, 2018 updated by: University Hospital, Bordeaux

Residual Immune Activation in HIV-infected Patients on Successful cART: Association Between Inflammasome Activation in Monocytes by Circulating Metabolites and Non AIDS Defining Comorbidities

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

55

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bordeaux, France
        • Service d'immunologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

HIV-infected patients with long-term suppressed viral load on cART

Description

HIV patients :

Inclusion Criteria:

  • Aged 18 years and above
  • HIV-1 infected patients
  • Enrolled in the CIADIS substudy of the ANRS CO3 Aquitaine cohort
  • Patients receiving antiretroviral therapy
  • HIV-1 RNA load below the detection limit of 40 copies/mL
  • With a written and signed informed consent

Exclusion Criteria:

  • HIV-2 or HIV-1/HIV-2 co-infection

Control patients :

Inclusion Criteria:

  • Aged 18 years and above

Exclusion Criteria:

  • HIV-1, HIV-2 or HIV-1/HIV-2 infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HIV patients
Other: blood sample
47ml blood (40 ml EDTA whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation and 7 ml for serum).
Control patients
Other: blood sample
47ml blood (40 ml EDTA whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation and 7 ml for serum).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of NLR (s) implicated in IL-18 up-regulation (inflammasome activation) in HIV
Time Frame: At baseline (D0)
  • The metabolic profile in purified monocytes from HIV patients through label-free proteomics and assignment of metabolic targets
  • The expression of NLR genes by quantitative Polymerase Chain Reaction (qPCR) in purified monocytes from HIV patients.
At baseline (D0)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of circulating metabolites that active the inflammasome machinery
Time Frame: At baseline (D0)
  • analysis of the ability of sera from HIV patients to activate inflammasome in HIV negative monocytes, and to induce IL-1, IL-18, or both secretion.
  • metabolomic profile
  • analysis of the ability of predominant metabolites in HIV patients to activate inflammasome.
At baseline (D0)
Non-AIDS related comorbidities
Time Frame: At baseline (D0)
metabolites of interest, inflammasome activation measured by IL-1b and IL-18
At baseline (D0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Collaborators

ANRS, Emerging Infectious Diseases
Sidaction
Centre National de la Recherche Scientifique, France

Investigators

  • Study Chair: Linda WITTKOP, MD, PhD, Université de Bordeaux - ISPED - Inserm 2129 - CHU de Bordeaux
  • Principal Investigator: Isabelle PELLEGRIN, MD, PhD, University Hospital, Bordeaux
  • Study Director: Benjamin FAUSTIN, PhD, Centre National de la Recherche Scientifique, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 3, 2017

Primary Completion (Actual)

December 20, 2017

Study Completion (Actual)

December 20, 2017

Study Registration Dates

First Submitted

June 14, 2017

First Submitted That Met QC Criteria

June 14, 2017

First Posted (Actual)

June 19, 2017

Study Record Updates

Last Update Posted (Actual)

September 28, 2018

Last Update Submitted That Met QC Criteria

September 27, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2016/14

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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