HIV ReservoirsINTESTIPAXNCT01942655
IL-23/IL-12 Imbalance and T Lymphocyte Polarization in HIV Infection
A study testing Blood sample and recto-colic biopsies in people with HIV Reservoirs, run by ANRS, Emerging Infectious Diseases at 1 site in France.
Trial summary
Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV Reservoirs
- What is being tested?
- Blood sample and recto-colic biopsies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jun 2014to 1 Mar 2018
- Phase
- Interventional
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Absence of coverage by French Health insurance system (Social Security)
- Known progressive malignancy
- Indeterminate colitis
- Known autoimmune diseases other than IBD
- Current chemotherapy or radiotherapy
- Vulnerable populations (children, pregnant women, persons under legal guardianship, or deprived of freedom by judicial or administrative decision)
Trial locations and contacts
1 site in 1 country.
France1 site
Centre d'Investigation Clinique BT505, Hôpital Cochin
Paris, 75014
About this study
Official title: ANRS RF002 Intestipax : Interleukin-23 (IL-23)/Interleukin-12 (IL-12) Imbalance and T Lymphocyte Polarization in HIV Infection
Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+ T cell loss and prognosis. The objectives of this project are to investigate the correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to study the polarization, infection or depletion of intestinal Th17 ex vivo. The investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
Read the detailed description
Th17 lymphocytes fight bacterial and fungal intestinal infections. Under combined antiretroviral therapy, even if the plasma viral load is undetectable, hyperactivation can persist, inducing localized replication from reservoirs. In humans, Th17 lymphocyte differentiation and expansion depend on IL-23. The investigators were the first to uncover an imbalance in the respective production of IL-12 and IL-23 in response to Lipopolysaccharide (LPS) in HIV-1 infected patients. IL-23 and its receptor are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD) like Crohn's disease, where the mucosa is altered by Th17 cells, inducing bacterial product translocation. IBD can be efficiently treated by antibodies directed against Tumor Necrosis Factor-α (TNF-α) or, in current clinical trials, against the p40 chain which is shared by IL-12 and IL-23. Unfortunately, these antibodies inhibit also IL-12. IL-12 is crucial against mycobacteria, which are opportunistic in HIV-infected patients. Antibodies directed against the p19 chain of IL-23 would inhibit Th17 activation more specifically.
The investigators will collect blood and recto-colic biopsies from 15 healthy donors, 15 HIV-infected patients with a viral load higher than 5000 copies/ml and 15 patients with evolutive IBD, to establish a parallel between the two diseases.
The objectives of this project are to study if there is a correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to investigate the polarization, infection or depletion of intestinal Th17 ex vivo. Investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
If these correlations are validated, the investigators will propose anti-IL-23 neutralizing treatment to allow Th17 and intestinal integrity to come back into balance, and therefore to break the vicious cycle of immune system hyperactivation drawn by bacterial translocation.
- Conditions
- HIV Reservoirs
- Being tested
- Blood sample and recto-colic biopsies
- Keywords
- HIV, Chronic inflammatory bowel disease, Reservoirs, IL-17, IL-23, Intestinal biopsies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sample and recto-colic biopsiesOther
| Study group | Role | What they receive |
|---|---|---|
| Patients with recto-colic biopsies prescribed | Experimental | 45 patients Receives: Other: Blood sample and recto-colic biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies.
Measured: 25 months
Secondary outcomes (1)
Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2013 (estimated)
- Study start1 Jun 2014
- Primary completion1 Mar 2018
- Study completion1 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV ReservoirsStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01942655
- Sponsor's protocol ID
- ANRS RF002 INTESTIPAX
- Acronym
- INTESTIPAX
- Status last verified
- Apr 2019
- First submitted
- 14 Aug 2013
- Last updated
- 30 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ANRS RF002 Intestipax : Interleukin-23 (IL-23)/Interleukin-12 (IL-12) Imbalance and T Lymphocyte Polarization in HIV Infection
- ClinicalTrials.gov ID
- NCT01942655
- Acronym / sponsor ID
- INTESTIPAX / ANRS RF002 INTESTIPAX
- Conditions
- HIV Reservoirs
- Keywords
- HIV, Chronic inflammatory bowel disease, Reservoirs, IL-17, IL-23, Intestinal biopsies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Study start
- 1 Jun 2014 (actual)
- Primary completion
- 1 Mar 2018 (actual)
- Study completion
- 1 Mar 2018 (actual)
- First posted
- 16 Sep 2013 (estimated)
- 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.
Progressive HIV or HIV infection seems to be related to a preferential loss of CD4+ T lymphocytes, especially Th17+, within the mucosal intestinal lymphoid tissue, and with intestinal mucosal damage and bacterial product translocation, which correlates with the hyperactivation of the immune system, therefore with CD4+ T cell loss and prognosis. The objectives of this project are to investigate the correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to study the polarization, infection or depletion of intestinal Th17 ex vivo. The investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
Detailed description
Th17 lymphocytes fight bacterial and fungal intestinal infections. Under combined antiretroviral therapy, even if the plasma viral load is undetectable, hyperactivation can persist, inducing localized replication from reservoirs. In humans, Th17 lymphocyte differentiation and expansion depend on IL-23. The investigators were the first to uncover an imbalance in the respective production of IL-12 and IL-23 in response to Lipopolysaccharide (LPS) in HIV-1 infected patients. IL-23 and its receptor are implicated in the pathogenesis of chronic inflammatory bowel diseases (IBD) like Crohn's disease, where the mucosa is altered by Th17 cells, inducing bacterial product translocation. IBD can be efficiently treated by antibodies directed against Tumor Necrosis Factor-α (TNF-α) or, in current clinical trials, against the p40 chain which is shared by IL-12 and IL-23. Unfortunately, these antibodies inhibit also IL-12. IL-12 is crucial against mycobacteria, which are opportunistic in HIV-infected patients. Antibodies directed against the p19 chain of IL-23 would inhibit Th17 activation more specifically.
The investigators will collect blood and recto-colic biopsies from 15 healthy donors, 15 HIV-infected patients with a viral load higher than 5000 copies/ml and 15 patients with evolutive IBD, to establish a parallel between the two diseases.
The objectives of this project are to study if there is a correlation between the IL12/IL-23 imbalance and bacterial product translocation, and to investigate the polarization, infection or depletion of intestinal Th17 ex vivo. Investigators will test the effect of neutralizing anti-IL23 antibodies directed against p40, or less classically, anti- IL-23 p19.
If these correlations are validated, the investigators will propose anti-IL-23 neutralizing treatment to allow Th17 and intestinal integrity to come back into balance, and therefore to break the vicious cycle of immune system hyperactivation drawn by bacterial translocation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with recto-colic biopsies prescribed | Experimental | Other: Blood sample and recto-colic biopsies45 patients |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Absence of coverage by French Health insurance system (Social Security)
- Known progressive malignancy
- Indeterminate colitis
- Known autoimmune diseases other than IBD
- Current chemotherapy or radiotherapy
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 sample and recto-colic biopsies | Other | Patients with recto-colic biopsies prescribed |
Primary outcome
Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies.
Time frame: 25 months
1 secondary outcome
Multiple measures : number of cells producing IL-23 and Th17 cells in intestinal biopsies
Time frame: 25 months
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 30 Apr 2019.
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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?
A study testing Blood sample and recto-colic biopsies in people with HIV Reservoirs, run by ANRS, Emerging Infectious Diseases 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 0 inclusion and 6 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 30 Apr 2019. 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?
Multiple measures: IL-17 and IL-23 producing cells in blood, and IL-17 and IL-23 coding mRNA in intestinal biopsies. (time frame: 25 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2019.