Human Immunodeficiency VirusInflammoVIHNCT03191175
Inflammasome Activation Via Circulating Metabolites
An observational study of Human Immunodeficiency Virus, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Human Immunodeficiency Virus
- What is being tested?
- blood sample
- How many people
- 55 participants
- Where
- 1 siteFrance
- Study dates
- 3 Jul 2017to 20 Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: HIV-infected patients with long-term suppressed viral load on cART
Who may be able to join
- 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
- Aged 18 years and above
Who cannot join
- HIV-2 or HIV-1/HIV-2 co-infection
- Control patients :
- HIV-1, HIV-2 or HIV-1/HIV-2 infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Human Immunodeficiency Virus
- Being tested
- blood sample
- Keywords
- HIV, Inflammasome
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleOther
47ml blood (40 ml EDTA whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation and 7 ml for serum).
| Study group | Role | What they receive |
|---|---|---|
| HIV patients | Not described Receives: Other: blood sample | |
| Control patients | Not described Receives: Other: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline (D0)
Secondary outcomes (2)
Characterization of circulating metabolites that active the inflammasome machinery
- 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.
Measured: At baseline (D0)
Non-AIDS related comorbidities
metabolites of interest, inflammasome activation measured by IL-1b and IL-18
Measured: At baseline (D0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2017
- Study start3 Jul 2017
- Primary completion20 Dec 2017
- Study completion20 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- ANRS, Emerging Infectious Diseases, Sidaction, Centre National de la Recherche Scientifique, France
- Responsible party
- Sponsor
- Investigators
- Linda WITTKOP, MD, PhD, Study chair, Université de Bordeaux - ISPED - Inserm 2129 - CHU de BordeauxIsabelle PELLEGRIN, MD, PhD, Principal investigator, University Hospital, BordeauxBenjamin FAUSTIN, PhD, Study director, Centre National de la Recherche Scientifique, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03191175
- Sponsor's protocol ID
- CHUBX 2016/14
- Acronym
- InflammoVIH
- Status last verified
- Sep 2018
- First submitted
- 14 Jun 2017
- Last updated
- 28 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 28092664Ozanne 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.
PubMed 28328797Duffau 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.
PubMed 26544576Wittkop 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.
PubMed 23204178
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Residual Immune Activation in HIV-infected Patients on Successful cART: Association Between Inflammasome Activation in Monocytes by Circulating Metabolites and Non AIDS Defining Comorbidities
- ClinicalTrials.gov ID
- NCT03191175
- Acronym / sponsor ID
- InflammoVIH / CHUBX 2016/14
- Conditions
- Human Immunodeficiency Virus
- Keywords
- HIV, Inflammasome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- ANRS, Emerging Infectious Diseases, Sidaction, Centre National de la Recherche Scientifique, France
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- 20 Dec 2017 (actual)
- Study completion
- 20 Dec 2017 (actual)
- First posted
- 19 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV patients | – | Other: blood sample |
| Control patients | – | Other: blood sample |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-infected patients with long-term suppressed viral load on cART
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- HIV-2 or HIV-1/HIV-2 co-infection
- HIV-1, HIV-2 or HIV-1/HIV-2 infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sample47ml blood (40 ml EDTA whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation and 7 ml for serum). | Other | Control patients, HIV patients |
Primary outcome
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.
2 secondary outcomes
Characterization of circulating metabolites that active the inflammasome machinery
Time frame: At baseline (D0)
Non-AIDS related comorbidities
Time frame: At baseline (D0)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2018.
- Background: PubMed 28092664Furman 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.
- Background: PubMed 28328797Ozanne 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.
- Background: PubMed 26544576Duffau 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.
- Background: PubMed 23204178Wittkop 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda WITTKOP, MD, PhD study chair
Université de Bordeaux - ISPED - Inserm 2129 - CHU de Bordeaux
Isabelle PELLEGRIN, MD, PhD principal investigator
University Hospital, Bordeaux
Benjamin FAUSTIN, PhD study director
Centre National de la Recherche Scientifique, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Immunodeficiency Virus, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of NLR (s) implicated in IL-18 up-regulation (inflammasome activation) in HIV (time frame: At baseline (D0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03191175, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2018.