HIV InfectionsMetACTIVIHNCT04028882
Immune Activation as a Cause of Insulin Resistance in Adults Living With HIV-1 on Effective Antiretroviral Therapy
An observational study of HIV Infections, run by University Hospital, Montpellier at 1 site in France.
Trial summary
The aim of this study is to characterize in non-viremic HIV-1 patients under antiretroviral therapy an immune activation profile that the investigators have previously shown to be strongly linked to hyperinsulinemia. This characterization will be carried out via 3 different approaches. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Signaling, metabolomic and transcriptomic analysis
- How many people
- 148 participants
- Where
- 1 siteFrance
- Study dates
- 3 Mar 2020to 9 Feb 2024
- 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
- No healthy volunteers
- Adult, Older adult
Study population: HIV-1-infected adults under efficient antiretroviral therapy
Who may be able to join
- Subject consulting or hospitalized in the tropical and infectious diseases unit at the University Hospital of Montpellier that have been enrolled in a study during which the immune activation profile was analyzed
- Subject aged at least 18 years
- Subject speaking french fluently
- Subject who is not opposed to participate to the study, after a clear information
- Subject affiliated to a social security system
- Infection by HIV-1 determined by a positive serology or by a measure of the plasma viral load (RNA HIV)
- HIV-1 patients under stable antiretroviral therapy
- HIV load < 50 copies/mL since at least 6 months before enrollment (2 measures)
Who cannot join
- Vulnerable individuals
- Persons protected
- Pregnant women or breastfeeding mothers
- Bad understanding of the nature and goals of the study and/or communication difficulties with the investigator
- Subject enrolled in an other study with an exclusion period still running
- Non infectious pathology that might be the origin of an immune anomaly
- Treatment by an immune modulator molecule or by chemotherapy in the 60 days before enrollment in the study
Trial locations and contacts
1 site in 1 country.
France1 site
Saint Eloi Hospital, University Hospital of Montpellier
Montpellier, Hérault, 34295
About this study
The aim of this study is to characterize in non-viremic HIV-1 patients under antiretroviral therapy an immune activation profile that the investigators have previously shown to be strongly linked to hyperinsulinemia. This characterization will be carried out via 3 different approaches. First, the investigators will analyze the metabolites present in the plasma of patients presenting with the profile of interest. Second, the investigators will study the transcriptome of the peripheral blood mononuclear cells of these patients. Finally, the investigators will search whether some factors released by these cells are able to induce insulin resistance. In addition the ability of the profile of interest to predict an increase in insulinemia over time will be assessed.
Read the detailed description
The working hypothesis of this study is that in efficiently treated HIV patients, various profiles of immune activation may be distinguished, each favouring particular comorbidities. Using a panel of 68 soluble and cell surface markers, the investigators have previously measured the level of activation in circulating Cluster of Differentiation 4+ (CD4+) and Cluster of Differentiation 8+ (CD8+), T cells, B cells, monocytes, Natural Killers (NK) cells, neutrophils, and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45 years of age. Two independent hierarchical clustering analyses allowed the investigators to identify five patient groups, each with the same activation profile. One of these profiles, Profile#2, was strongly associated with hyperinsulinemia (Psomas et al., 2016).
The main objective of the present study is to better define Profile#2. To this aim, the investigators will analyze by mass spectrometry the metabolites in the plasma of patients with various profiles including the one of interest. Concurrently, the investigators will perform an RiboNucleic Acid Sequencing (RNASeq) analysis on peripheral blood mononuclear cells (PBMC) from the same patients. These metabolomic and transcriptomic data will help to better define the immune activation profiles.
The secondary objective is to test whether the link the investigators have observed between Profile#2 and insulin resistance is causative. To this aim, by following over time patients' insulinemia, the investigators will test whether Profile#2 is predictive of an increase in insulinemia. The investigators will also look for factors released by PBMC of patients with Profile#2 able to induce insulin resistance.
- Conditions
- HIV Infections
- Being tested
- Signaling, metabolomic and transcriptomic analysis
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Signaling, metabolomic and transcriptomic analysisOther
Signaling, metabolomic and transcriptomic analysis
| Study group | Role | What they receive |
|---|---|---|
| Non viremic HIV patients under treatment | Patients with various immune activation profiles Receives: Other: Signaling, metabolomic and transcriptomic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolomic analysis on plasma and PBMC
The investigators will analyze by mass spectrometry the metabolites present in the plasma of patients presenting with the profile of interest as compared with patients with other immune activation profiles. Metabolites will be extracted from the blood plasma using a salt assisted liquid-liquid extraction. The metabolites will then be allowed to crystallize on the metallic surface. Finally, the plate content will be analyzed by desorption electrospray ionisation mass spectrometry using positive and negative ionization.
Measured: 18 months
Transcriptomic analysis on plasma and PBMC
The investigators will also analyze by RNASeq the messenger RNA (mRNA) produced by the PBMC of patients presenting with the profile of interest and compared them with the mRNA produced by the PBMC of patients with other immune activation profiles.
Measured: 18 months
Secondary outcomes (2)
Follow-up over time of insulinemia in patients with various immune activation profiles
The investigators will compare over time the increase in insulinemia in patients presenting or not the immune activation profile of interest.
Measured: 18 months
Test whether PBMC from patients with Profile#2 induce insulin resistance
The investigators will analyze whether PBMC from patients with the immune activation profile of interest release factors able to inhibit insulin signaling in hepatocytes. Insulin signaling will be measured by quantifying Akt phosphorylation vie western blot.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start3 Mar 2020
- Primary completion9 Feb 2024
- Study completion9 Feb 2024
Why it stopped: Preliminary analyses regarding the main objective show negative results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04028882
- Sponsor's protocol ID
- RECHMPL18_0373
- Acronym
- MetACTIVIH
- Status last verified
- Aug 2024
- First submitted
- 12 Jun 2019
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Psomas C, Younas M, Reynes C, Cezar R, Portales P, Tuaillon E, Guigues A, Merle C, Atoui N, Fernandez C, Le Moing V, Barbuat C, Marin G, Nagot N, Sotto A, Eliaou JF, Sabatier R, Reynes J, Corbeau P. One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study. EBioMedicine. 2016 Jun;8:265-276. doi: 10.1016/j.ebiom.2016.05.008. Epub 2016 May 10.
PubMed 27428436Younas M, Gimenez S, Lin YL, Mettling C, Maiorano D, Reynes J, Pasero P, Rondard P, Psomas CK, Corbeau P. gamma-Aminobutyric Acid-Induced Monocytic Reactive Oxygen Species Impair CD4 Restoration in Treated Adults With HIV-1. J Infect Dis. 2025 Jun 2;231(5):1246-1257. doi: 10.1093/infdis/jiaf058.
PubMed 39903648
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Activation as a Cause of Insulin Resistance in Adults Living With HIV-1 on Effective Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT04028882
- Acronym / sponsor ID
- MetACTIVIH / RECHMPL18_0373
- Conditions
- HIV Infections
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Preliminary analyses regarding the main objective show negative results
- Enrolment
- 148 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 9 Feb 2024 (actual)
- Study completion
- 9 Feb 2024 (actual)
- First posted
- 23 Jul 2019 (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 aim of this study is to characterize in non-viremic HIV-1 patients under antiretroviral therapy an immune activation profile that the investigators have previously shown to be strongly linked to hyperinsulinemia. This characterization will be carried out via 3 different approaches. First, the investigators will analyze the metabolites present in the plasma of patients presenting with the profile of interest. Second, the investigators will study the transcriptome of the peripheral blood mononuclear cells of these patients. Finally, the investigators will search whether some factors released by these cells are able to induce insulin resistance. In addition the ability of the profile of interest to predict an increase in insulinemia over time will be assessed.
Detailed description
The working hypothesis of this study is that in efficiently treated HIV patients, various profiles of immune activation may be distinguished, each favouring particular comorbidities. Using a panel of 68 soluble and cell surface markers, the investigators have previously measured the level of activation in circulating Cluster of Differentiation 4+ (CD4+) and Cluster of Differentiation 8+ (CD8+), T cells, B cells, monocytes, Natural Killers (NK) cells, neutrophils, and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45 years of age. Two independent hierarchical clustering analyses allowed the investigators to identify five patient groups, each with the same activation profile. One of these profiles, Profile#2, was strongly associated with hyperinsulinemia (Psomas et al., 2016).
The main objective of the present study is to better define Profile#2. To this aim, the investigators will analyze by mass spectrometry the metabolites in the plasma of patients with various profiles including the one of interest. Concurrently, the investigators will perform an RiboNucleic Acid Sequencing (RNASeq) analysis on peripheral blood mononuclear cells (PBMC) from the same patients. These metabolomic and transcriptomic data will help to better define the immune activation profiles.
The secondary objective is to test whether the link the investigators have observed between Profile#2 and insulin resistance is causative. To this aim, by following over time patients' insulinemia, the investigators will test whether Profile#2 is predictive of an increase in insulinemia. The investigators will also look for factors released by PBMC of patients with Profile#2 able to induce insulin resistance.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non viremic HIV patients under treatment | – | Other: Signaling, metabolomic and transcriptomic analysisPatients with various immune activation profiles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-1-infected adults under efficient antiretroviral therapy
Key inclusion criteria (8 listed)
- Subject consulting or hospitalized in the tropical and infectious diseases unit at the University Hospital of Montpellier that have been enrolled in a study during which the immune activation profile was analyzed
- Subject aged at least 18 years
- Subject speaking french fluently
- Subject who is not opposed to participate to the study, after a clear information
- Subject affiliated to a social security system
Key exclusion criteria (7 listed)
- Vulnerable individuals
- Persons protected
- Pregnant women or breastfeeding mothers
- Bad understanding of the nature and goals of the study and/or communication difficulties with the investigator
- Subject enrolled in an other study with an exclusion period still running
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 |
|---|---|---|
| Signaling, metabolomic and transcriptomic analysisSignaling, metabolomic and transcriptomic analysis | Other | Non viremic HIV patients under treatment |
Primary outcome
Metabolomic analysis on plasma and PBMC
Time frame: 18 months
The investigators will analyze by mass spectrometry the metabolites present in the plasma of patients presenting with the profile of interest as compared with patients with other immune activation profiles. Metabolites will be extracted from the blood plasma using a salt assisted liquid-liquid extraction. The metabolites will then be allowed to crystallize on the metallic surface. Finally, the plate content will be analyzed by desorption electrospray ionisation mass spectrometry using positive and negative ionization.
Transcriptomic analysis on plasma and PBMC
Time frame: 18 months
The investigators will also analyze by RNASeq the messenger RNA (mRNA) produced by the PBMC of patients presenting with the profile of interest and compared them with the mRNA produced by the PBMC of patients with other immune activation profiles.
2 secondary outcomes
Follow-up over time of insulinemia in patients with various immune activation profiles
Time frame: 18 months
Test whether PBMC from patients with Profile#2 induce insulin resistance
Time frame: 18 months
Results and safety
The study was stopped early (reason given: Preliminary analyses regarding the main objective show negative results). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Background: PubMed 27428436Psomas C, Younas M, Reynes C, Cezar R, Portales P, Tuaillon E, Guigues A, Merle C, Atoui N, Fernandez C, Le Moing V, Barbuat C, Marin G, Nagot N, Sotto A, Eliaou JF, Sabatier R, Reynes J, Corbeau P. One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study. EBioMedicine. 2016 Jun;8:265-276. doi: 10.1016/j.ebiom.2016.05.008. Epub 2016 May 10.
- Derived from this study: PubMed 39903648Younas M, Gimenez S, Lin YL, Mettling C, Maiorano D, Reynes J, Pasero P, Rondard P, Psomas CK, Corbeau P. gamma-Aminobutyric Acid-Induced Monocytic Reactive Oxygen Species Impair CD4 Restoration in Treated Adults With HIV-1. J Infect Dis. 2025 Jun 2;231(5):1246-1257. doi: 10.1093/infdis/jiaf058.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 HIV Infections, run by University Hospital, Montpellier 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 8 inclusion and 7 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: stopped early, as of the sponsor's last update on 6 Aug 2024. 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 was stopped early (reason given: Preliminary analyses regarding the main objective show negative results). Results are not available in the source record.
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?
Metabolomic analysis on plasma and PBMC (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT04028882, which also lists 2 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 6 Aug 2024.