Inflammasome Activation Via Circulating Metabolites

NCT03191175 | Completed

• 1 other identifier: CHUBX 2016/14
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

HIV; Inflammasome

Outcome Measures

Primary Outcomes (1)

• Characterization of NLR (s) implicated in IL-18 up-regulation (inflammasome activation) in HIV

  * 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 Outcomes (2)

• Characterization of circulating metabolites that active the inflammasome machinery

  At baseline (D0)

• Non-AIDS related comorbidities

  At baseline (D0)

Study Arms (2)

HIV patients

Other: blood sample

Control patients

Other: blood sample

Interventions

blood sample OTHER

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

Control patients; HIV patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• HIV-2 or HIV-1/HIV-2 co-infection
• Control patients :
• Aged 18 years and above
• HIV-1, HIV-2 or HIV-1/HIV-2 infection

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• ANRS, Emerging Infectious Diseases: collaborator
• Sidaction: collaborator
• Centre National de la Recherche Scientifique, France: collaborator

Study Sites (1)

Service d'immunologie

Bordeaux, France

Location

Related Publications (4)

• Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Dechanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat Med. 2017 Feb;23(2):174-184. doi: 10.1038/nm.4267. Epub 2017 Jan 16.

  PMID: 28092664 BACKGROUND

• Ozanne A, Duffau P, Dauchy FA, Rigothier C, Terrien C, Lazaro E, Cazanave C, Lawson-Ayayi S, Bonnet F, Blanco P, Wittkop L, Pellegrin I; CIADIS sub-study in the ANRS CO3 Aquitaine cohort study group. Activation, senescence and inflammation markers in HIV patients: association with renal function. AIDS. 2017 May 15;31(8):1119-1128. doi: 10.1097/QAD.0000000000001461.

  PMID: 28328797 BACKGROUND

• Duffau P, Wittkop L, Lazaro E, le Marec F, Cognet C, Blanco P, Moreau JF, Dauchy FA, Cazanave C, Vandenhende MA, Bonnet F, Thiebaut R, Pellegrin I; ANRS CO3 Aquitaine Cohort Study Group. Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients. AIDS. 2015 Oct 23;29(16):2099-108. doi: 10.1097/QAD.0000000000000807.

  PMID: 26544576 BACKGROUND

• Wittkop L, Bitard J, Lazaro E, Neau D, Bonnet F, Mercie P, Dupon M, Hessamfar M, Ventura M, Malvy D, Dabis F, Pellegrin JL, Moreau JF, Thiebaut R, Pellegrin I; Groupe d'Epidemiologie Clinique du SIDA en Aquitaine. Effect of cytomegalovirus-induced immune response, self antigen-induced immune response, and microbial translocation on chronic immune activation in successfully treated HIV type 1-infected patients: the ANRS CO3 Aquitaine Cohort. J Infect Dis. 2013 Feb 15;207(4):622-7. doi: 10.1093/infdis/jis732. Epub 2012 Nov 29.

  PMID: 23204178 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood sampling

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Linda WITTKOP, MD, PhD

  Université de Bordeaux - ISPED - Inserm 2129 - CHU de Bordeaux

  STUDY CHAIR

• Isabelle PELLEGRIN, MD, PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Benjamin FAUSTIN, PhD

  Centre National de la Recherche Scientifique, France

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 19, 2017
• Study Start: July 3, 2017
• Primary Completion: December 20, 2017
• Study Completion: December 20, 2017
• Last Updated: September 28, 2018

Record last verified: 2018-09

Locations

FR (1)