HIV InfectionsPREDIACCNCT04208711
Role of PLA2G1B During HIV Infection
A study testing biological sample in people with HIV Infections, run by Diaccurate SAS at 1 site in France.
Trial summary
The main objective of this study is to qualify and quantify, by microscopy techniques, CD4+ lymphocyte abnormalities during HIV infection in 7 patients who are naive to any ARV (antiretroviral ) treatment and secondarily to follow the kinetics of reversion of the observed abnormalities, as well as the evolution of the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- biological sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteFrance
- Study dates
- 1 Mar 2019to Mar 2022
- 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
- Participant aged 18 to under 70
- Participant having signed the written and informed consent;
- Patient with HIV-1 infection documented by a positive HIV western blot positive (infected patients> 6 months, CD4 count> 350 / mm3 and HIV RNA <100.000 copies / mL) naive to any ARV treatment Anti-HIV antibody positive and an optical density <1.0, as determined by enzyme immunoassay, with no significant risk of clinical events
- Appropriate laboratory data: hemoglobin> 9 g / dL, absolute neutrophil count ≥1000 / μL, platelets ≥50,000 / μL, bilirubin ≤ 1.5 X upper limit of normal (ULN) or ≤3 X ULN serum creatinine ≤ 1.5 X ULN, alanine amino transferase (ALT) or aspartate amino transferase (AST) ≤ 3 X ULN;
- ECOG (Eastern Cooperative Oncology Group) performance status scale ≤2
- Subject benefiting from a French social security scheme, or affiliated to such a scheme
Who cannot join
- History of inflammatory disease such as rheumatoid arthritis, lupus, Crohn's disease, ulcerative colitis
- Concomitant use of systemic or topical corticosteroids for the treatment of skin diseases. However, topical steroids and oral steroids (≤10 mg prednisone equivalent / day) are permitted if the patient has received a stable dose with stable symptoms for at least 4 weeks before inclusion in the study.
- Major surgery <4 weeks before inclusion in the study.
- A stem cell transplant.
- History of other malignancies in the last three years except Kaposi controlled.
- Infection known by hepatitis C or B virus (HCV or HBV)
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- Congestive heart failure, class III or IV, according to the criteria of the New York Heart Association (NYHA).
- Vulnerable population (minors, pregnant, parturient or nursing women, persons under guardianship or trusteeship, or deprived of liberty by a judicial or administrative decision, under the protection of justice)
- Patients with dementia or altered mental states who would not understand and provide an informed consent document
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CIC 1417 Cochin Pasteur, hôpital Cochin
Paris, 75014
LAUNAY, odile.launay@aphp.fr
KONATE, +33(0) 1 58 41 33 68, eleine.konate@aphp.fr
About this study
Official title: Study of the Role of PLA2G1B in the Immunopathogenicity by Action on CD4 T Cells During HIV Infection
The main objective of this study is to qualify and quantify, by microscopy techniques, CD4+ lymphocyte abnormalities during HIV infection in 7 patients who are naive to any ARV (antiretroviral ) treatment and secondarily to follow the kinetics of reversion of the observed abnormalities, as well as the evolution of the levels of PLA2G1B and its cofactor gp41 in 8 patients under ARV treatment
Read the detailed description
Antiretroviral therapy in HIV-infected patients has progressed significantly over the past two decades.
Viral replication in patients who are complicit in their treatment regimen is greatly reduced below detection limits (quantification) by current and approved laboratory tests. However, the persistence of residual (plasma) replication of the virus creates an inflammatory state associated with certain pathologies, accelerated aging and premature mortality. If treatment is discontinued for any reason, viral replication resumes within a few weeks in almost all patients.
Alternative infections of inflammatory pathways in HIV can also play a critical role in the inflammatory process suppressed by treatment. Members of the phospholipase A2 family can hydrolyze phospholipid molecules at the sn-2 position, making it a question about lipid moieties. One of the members, the phospholipase A2 group1B (PLA2G1B), is found in the plasma of HIV-infected patients who are not receiving antiretroviral therapy. Ex vivo, this enzyme is able to induce a purified CD4 lymphocyte energy from donors, as well as by inducing the lack of response to IL-7 (interleukin-7). In the long term, loss of response to IL-7 induces CD4 lymphopenia. Therefore, PLA2G1B must play an important role in the mechanism leading to HIV-infected patients becoming immunodeficient.
At the clinical level, we found that PLA2G1B activity increases in all HIV-infected patients and decreases after ARV treatment. On the other hand, for patients who are able to eliminate the HIV virus on therapy but whose immunological response remains low, PLA2G1B activity remains high. More interestingly, in "HIV Elite Controller" patients, PLA2G1B activity is not found in their plasma. Overall, there is a correlation between the different clinical groups (viremic not on therapy, ARV and virus removal with robust CD4+ T-cell response, virus removal with suboptimal CD4+ T-cell response and "HIV Elite Controller") and the activity level of PLA2G1B in their plasma.
The purpose of this study, more generally, is to study the role of PLA2G1B in CD4 lymphocytes and to analyze the reversion of its effects in the immunopathogenicity of HIV infection.
In the main study, 15 patients will be included. The analysis of the first 7 patients will in addition meet the objectives of the study, to determine the test that will allow the follow-up of the 8 other patients after ARV treatment. The participation of the 7 patients in the study is limited to 1 (one) day.
In the sub-study, the last 8 patients following their inclusion in the main study will enter a follow-up phase of 12 months after they are put on ARV treatment. The total duration of participation for the 8 patients will be 13 months.
The main study is carried out by taking 50 mL of total blood and in the sub-study, 30mL of blood sample will be taken during the follow-up visit (at M1, M3, M6, M9 and 12 Months) after ARV treatment.
- Conditions
- HIV Infections
- Being tested
- biological sample
- Keywords
- HIV infection, PLA2G1B, Lymphocyte CD4+
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biological sampleOther
whole blood sample
| Study group | Role | What they receive |
|---|---|---|
| positive HIV patient not treated by ARV yet | Other | Before starting HIV treatment, 15 patients will be included in the study and 50mL of whole blood will be taken. After treatment initiation 8 of the 15 patients will entered in the follow-up phase for 1 year (5 followup visit, M1, M3, M6, M9, M12) and 30mL of whole blood will be taken at each visit.
The duration of the study for the 7 other patients will be 1 day. Receives: Other: biological sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
immunological : to qualify and quantify by confocal microscopic techniques and flow cytometry lymphocyte abnormalities
The assessment of the change in the proportion of lymphocytes at 1, 3, 6, 9 and 12 months as compared to Day 1:
- CD4 with membranes abnormalities above normal,
- CD4 with major membrane abnormalities,
- CD4 with signal transduction abnormalities,
- CD4 reversing one of these abnormalities spontaneously or after treatment with neutralizing monoclonal antibody (mAb) 2B2
Measured: up to 1 year
Secondary outcomes (1)
immunological
The assessment by immunophenotyping test ( flow cytometry) of the change at 1, 3, 6, 9 and 12 months as compared to Day 1 of:
- number of CD4/mm3 of blood, number of CD8/mm3 of blood, CD4 / CD8 ratio, viral load (copies of HIV RNA/mL of blood), viral DNA (copies of HIV DNA/mL of blood)
- number of CD4/mm3 secreting IFN gamma (Interferon gamma), TNF (Tumor necrosis factor) and IL-2 (Interleukin-2) (in % of IFN - TNFa - IL-2+ / CD4)
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2019
- Study start1 Mar 2019
- Primary completionMar 2022 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Diaccurate SAS
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CIC 1417 Cochin-Pasteur
- Responsible party
- Sponsor
- Investigators
- Odile LAUNAY, MD, PHD, Principal investigator, CIC 1417 Clinical Center Investigation - Cochin Hospital, AP-HP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04208711
- Sponsor's protocol ID
- PREDIACC
- Other IDs
- 2018-A02025-50
- Acronym
- PREDIACC
- Status last verified
- Feb 2021
- First submitted
- 2 Dec 2019
- Last updated
- 8 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Role of PLA2G1B in the Immunopathogenicity by Action on CD4 T Cells During HIV Infection
- ClinicalTrials.gov ID
- NCT04208711
- Acronym / sponsor ID
- PREDIACC / PREDIACC
- Conditions
- HIV Infections
- Keywords
- HIV infection, PLA2G1B, Lymphocyte CD4+
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Diaccurate SASIndustry (pharma, biotech, devices)
- Collaborators
- CIC 1417 Cochin-Pasteur
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- Mar 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 23 Dec 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 main objective of this study is to qualify and quantify, by microscopy techniques, CD4+ lymphocyte abnormalities during HIV infection in 7 patients who are naive to any ARV (antiretroviral ) treatment and secondarily to follow the kinetics of reversion of the observed abnormalities, as well as the evolution of the levels of PLA2G1B and its cofactor gp41 in 8 patients under ARV treatment
Detailed description
Antiretroviral therapy in HIV-infected patients has progressed significantly over the past two decades.
Viral replication in patients who are complicit in their treatment regimen is greatly reduced below detection limits (quantification) by current and approved laboratory tests. However, the persistence of residual (plasma) replication of the virus creates an inflammatory state associated with certain pathologies, accelerated aging and premature mortality. If treatment is discontinued for any reason, viral replication resumes within a few weeks in almost all patients.
Alternative infections of inflammatory pathways in HIV can also play a critical role in the inflammatory process suppressed by treatment. Members of the phospholipase A2 family can hydrolyze phospholipid molecules at the sn-2 position, making it a question about lipid moieties. One of the members, the phospholipase A2 group1B (PLA2G1B), is found in the plasma of HIV-infected patients who are not receiving antiretroviral therapy. Ex vivo, this enzyme is able to induce a purified CD4 lymphocyte energy from donors, as well as by inducing the lack of response to IL-7 (interleukin-7). In the long term, loss of response to IL-7 induces CD4 lymphopenia. Therefore, PLA2G1B must play an important role in the mechanism leading to HIV-infected patients becoming immunodeficient.
At the clinical level, we found that PLA2G1B activity increases in all HIV-infected patients and decreases after ARV treatment. On the other hand, for patients who are able to eliminate the HIV virus on therapy but whose immunological response remains low, PLA2G1B activity remains high. More interestingly, in "HIV Elite Controller" patients, PLA2G1B activity is not found in their plasma. Overall, there is a correlation between the different clinical groups (viremic not on therapy, ARV and virus removal with robust CD4+ T-cell response, virus removal with suboptimal CD4+ T-cell response and "HIV Elite Controller") and the activity level of PLA2G1B in their plasma.
The purpose of this study, more generally, is to study the role of PLA2G1B in CD4 lymphocytes and to analyze the reversion of its effects in the immunopathogenicity of HIV infection.
In the main study, 15 patients will be included. The analysis of the first 7 patients will in addition meet the objectives of the study, to determine the test that will allow the follow-up of the 8 other patients after ARV treatment. The participation of the 7 patients in the study is limited to 1 (one) day.
In the sub-study, the last 8 patients following their inclusion in the main study will enter a follow-up phase of 12 months after they are put on ARV treatment. The total duration of participation for the 8 patients will be 13 months.
The main study is carried out by taking 50 mL of total blood and in the sub-study, 30mL of blood sample will be taken during the follow-up visit (at M1, M3, M6, M9 and 12 Months) after ARV treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| positive HIV patient not treated by ARV yet | Other | Other: biological sampleBefore starting HIV treatment, 15 patients will be included in the study and 50mL of whole blood will be taken. After treatment initiation 8 of the 15 patients will entered in the follow-up phase for 1 year (5 followup visit, M1, M3, M6, M9, M12) and 30mL of whole blood will be taken at each visit. The duration of the study for the 7 other patients will be 1 day. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participant aged 18 to under 70
- Participant having signed the written and informed consent;
- Patient with HIV-1 infection documented by a positive HIV western blot positive (infected patients> 6 months, CD4 count> 350 / mm3 and HIV RNA <100.000 copies / mL) naive to any ARV treatment Anti-HIV antibody positive and an optical density <1.0, as determined by enzyme immunoassay, with no significant risk of clinical events
- Appropriate laboratory data: hemoglobin> 9 g / dL, absolute neutrophil count ≥1000 / μL, platelets ≥50,000 / μL, bilirubin ≤ 1.5 X upper limit of normal (ULN) or ≤3 X ULN serum creatinine ≤ 1.5 X ULN, alanine amino transferase (ALT) or aspartate amino transferase (AST) ≤ 3 X ULN;
- ECOG (Eastern Cooperative Oncology Group) performance status scale ≤2
Key exclusion criteria (9 listed)
- History of inflammatory disease such as rheumatoid arthritis, lupus, Crohn's disease, ulcerative colitis
- Concomitant use of systemic or topical corticosteroids for the treatment of skin diseases. However, topical steroids and oral steroids (≤10 mg prednisone equivalent / day) are permitted if the patient has received a stable dose with stable symptoms for at least 4 weeks before inclusion in the study.
- Major surgery <4 weeks before inclusion in the study.
- A stem cell transplant.
- History of other malignancies in the last three years except Kaposi controlled.
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 |
|---|---|---|
| biological samplewhole blood sample | Other | positive HIV patient not treated by ARV yet |
Primary outcome
immunological : to qualify and quantify by confocal microscopic techniques and flow cytometry lymphocyte abnormalities
Time frame: up to 1 year
The assessment of the change in the proportion of lymphocytes at 1, 3, 6, 9 and 12 months as compared to Day 1: * CD4 with membranes abnormalities above normal, * CD4 with major membrane abnormalities, * CD4 with signal transduction abnormalities, * CD4 reversing one of these abnormalities spontaneously or after treatment with neutralizing monoclonal antibody (mAb) 2B2
1 secondary outcome
immunological
Time frame: up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2021.
- 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.
Odile LAUNAY, MD, PHD principal investigator
CIC 1417 Clinical Center Investigation - Cochin Hospital, AP-HP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing biological sample in people with HIV Infections, run by Diaccurate SAS 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 6 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 8 Feb 2021. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact THEZE (+33(0) 1 45 68 86 00, jacques.theze@diaccurate.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
immunological : to qualify and quantify by confocal microscopic techniques and flow cytometry lymphocyte abnormalities (time frame: up to 1 year). 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 8 Feb 2021.