HIV InfectionEP 45NCT01038999
Accelerated Aging, HIV Infection, Antiretroviral Therapies
An observational study of HIV Infection and Aging Accelerated, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
Trial summary
The main goal is to confirm, among HIV1-infected patients, data from in vitro studies showing that antiretroviral therapies induce an accelerated aging through the same mechanisms than genetic laminopathies or than "physiological " aging, that is through the synthesis and persistence of farnesylated prelamin A. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infection, Aging Accelerated, Antiretroviral Therapies
- What is being tested?
- Peripheral blood biological tests
- How many people
- 200 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2009to Mar 2012
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 50 HIV1-infected naive patients (A group), apparied to 50 age- and sex-matched seronegative control (C group) subjects and 100 HIV1-infected patients in first line of antiretroviral therapy for at least 12 months (B group)
Who may be able to join
- Age ≥ 18 years and <65 years Able to give written consent Covered by French Social Security Non infected by HIV-2
- - A group HIV1-infected naive patients
- -B group infected patients in first line of antiretroviral therapy for at least 12 months
- -C group HIV seronegative Confirmed by a fast test of screening of the HIV at day one of study
Who cannot join
- Age < 18 years and > 65 years
- Not Able to give written consent
- Not Covered by French Social Security
- Infected by HIV-2
- treated by statin or biphosphonat amino
- concomitant treatment: diabetic or testosteron
Trial locations and contacts
1 site in 1 country.
France1 site
ANRS center from Marseille, Timone and Montpellier and Nice
Country of French
About this study
The main goal is to confirm, among HIV1-infected patients, data from in vitro studies showing that antiretroviral therapies induce an accelerated aging through the same mechanisms than genetic laminopathies or than "physiological " aging, that is through the synthesis and persistence of farnesylated prelamin A. The secondary goal is to measure the impact of HIV infection and of antiretroviral therapies on markers of cell ageing (proteasome, mitochondria, telomere). The perspective is to fix antiretroviral therapy side effects using the same drug combination that will be used in few weeks in Marseille to treat children suffering from progeria
Read the detailed description
Protease inhibitors block viral protease, as well as various other cell enzymes : ZMPSTE24 cliping off prelamin A into mature lamin A ; at least one of the Golgi proteases involved in the release of SREBP, controlling the transcription of lipid metabolism regulating genes ; mitochondrial proteases involved in the importation and further maturation of nuclear genome encoded proteins ; proteasome regulating the transcription of several genes through NF-B ; P450 cytochromes. Nucleosides inhibitors of the viral reverse transcriptase exhibit nuclear and mitochondrial DNA toxicity, disrupt lipid and protein glycosylation and inhibit telomerase. Therefore antiretroviral therapies target several pathways involved in accelerated or normal aging. Their combined effects are added to viral infection direct symptoms or to cell abnormalities induced by viral proteins.
Our multicentric (the 3 CISIH from Marseille, Nice and Montpellier) 3 year- long study will analyse 50 HIV1-infected naive patients (A group), apparied to 50 age- and sex-matched seronegative control subjects (recruited by CIC-UPCET of Marseille) and 100 HIV1-infected patients in first line of antiretroviral therapy for at least 12 months (B group). Patients of group A and B will be recruited in the 3 clinical unit. The HIV1- infected patients will be evaluated four times, at baseline, then every 12 months during 3 years. In case of initiation or changing of antiretroviral therapy, patients will be evaluated once more. Control subjects will be only evaluated at baseline.
Peripheral blood biological tests will be the following [Laboratory designation] : i/ viral load measurement, PBMC isolation, DNA extraction, proviral DNA measurement, cell and DNA storage [Virology, Timone CHU, Marseille]; ii/ assays of CD4, CD8, glycemia, insulinemia, HOMA, total-, LDL- and HDL-cholesterol, triglycerides [Biochemistry labs from the 3 CHU] ; iii/ antiretroviral drug assay (mass spectrometry) [Pharmacokinetics, Timone CHU, Marseille]; iv/ detection (western blotting, immunocytochemistry combined to image analysis of nuclear abnormalities) of PBMC nuclear, cytosolic and mitochondrial targets of antiretroviral drugs : A and B lamins, NF-B + I-B and proteasome activity assay, CD36 (glycosylation), mitochondrial Hsp70, ROS mitochondrial production, mitochondrial inner membrane potential, cytochrome C oxidase subunits 2 and 4 [Cell Biology, Timone CHU, Marseille] ; v/ genotyping the antiretroviral targets : lamin A (ZMPSTE24) and B (Rce1) processing proteases, Golgi SREBP-releasing proteases (MBTPS1 and S2), mitochondrial deoxynucleoside transporters (SLC25A4 to A6), mitochondrial proteases (MPPA, paraplegin) involved in processing of nuclear encoded proteins during their mitochondrial import ; quantitative PCR measurement of telomere length [Molecular Genetics, Timone CHU, Marseille]. Marseille's CIC-UPCET collaborated to the protocol design, will recruit control subjects and will be responsible for statistical treatment of data.
- Conditions
- HIV Infection, Aging Accelerated, Antiretroviral Therapies
- Being tested
- Peripheral blood biological tests
- Keywords
- Complementary Therapies
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peripheral blood biological testsBiological
A group and B group will be evaluated three times, at baseline, then every 12 months during 3 years. In case of initiation or changing of antiretroviral therapy, patients will be evaluated once more. Control subjects will be only evaluated at baseline.
| Study group | Role | What they receive |
|---|---|---|
| A HIV1-infected naive patients | Not described Receives: Biological: Peripheral blood biological tests | |
| B HIV1-infected patients | in 1st line of ARV therapy for at least 12 months Receives: Biological: Peripheral blood biological tests | |
| C= control Non infected HIV volunters | Not described Receives: Biological: Peripheral blood biological tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
lamin A measurement by western blotting
Secondary outcomes (1)
Peripheral blood biological tests (cellular, molecular genetic)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2009 (estimated)
- Study startApr 2009
- Primary completionApr 2010
- Study completionMar 2012
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 InfectionStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Investigators
- Isabelle POIZOT-MARTIN, Principal investigator, CHU Sainte Marguerite -MarseilleMarie-Pierre DROGOUL, Principal investigator, CHU Sainte Marguerite -MarseilleOlivia FAUCHER, Principal investigator, CHU Sainte Marguerite -MarseilleAmélie MENARD, Principal investigator, CHU Sainte Marguerite -MarseilleJoëlle MICALLEF-ROLL, Principal investigator, CHU TimoneJacques REYNES, Principal investigator, CISIH CHRU Gui de Chauliac- MontpellierPierre DELLAMONICA, Principal investigator, CISIH CHU NicePierre CAU, Principal investigator, INSERM UMR S910 MARSEILLE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01038999
- Sponsor's protocol ID
- 2008-A00905-50
- Acronym
- EP 45
- Status last verified
- Dec 2012
- First submitted
- 23 Dec 2009
- Last updated
- 27 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Perrin S, Cremer J, Faucher O, Reynes J, Dellamonica P, Micallef J, Solas C, Lacarelle B, Stretti C, Kaspi E, Robaglia-Schlupp A, Nicolino-Brunet C, Tamalet C, Levy N, Poizot-Martin I, Cau P, Roll P. HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. PLoS One. 2012;7(12):e53035. doi: 10.1371/journal.pone.0053035. Epub 2012 Dec 28.
PubMed 23285253Perrin S, Cremer J, Roll P, Faucher O, Menard A, Reynes J, Dellamonica P, Naqvi A, Micallef J, Jouve E, Tamalet C, Solas C, Pissier C, Arnoux I, Nicolino-Brunet C, Espinosa L, Levy N, Kaspi E, Robaglia-Schlupp A, Poizot-Martin I, Cau P. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 "Aging" study. PLoS One. 2012;7(7):e41129. doi: 10.1371/journal.pone.0041129. Epub 2012 Jul 19.
PubMed 22829920
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated Aging, HIV Infection, Antiretroviral Therapies
- ClinicalTrials.gov ID
- NCT01038999
- Acronym / sponsor ID
- EP 45 / 2008-A00905-50
- Conditions
- HIV Infection, Aging Accelerated, Antiretroviral Therapies
- Keywords
- Complementary Therapies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Study start
- Apr 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 24 Dec 2009 (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.
The main goal is to confirm, among HIV1-infected patients, data from in vitro studies showing that antiretroviral therapies induce an accelerated aging through the same mechanisms than genetic laminopathies or than "physiological " aging, that is through the synthesis and persistence of farnesylated prelamin A. The secondary goal is to measure the impact of HIV infection and of antiretroviral therapies on markers of cell ageing (proteasome, mitochondria, telomere). The perspective is to fix antiretroviral therapy side effects using the same drug combination that will be used in few weeks in Marseille to treat children suffering from progeria
Detailed description
Protease inhibitors block viral protease, as well as various other cell enzymes : ZMPSTE24 cliping off prelamin A into mature lamin A ; at least one of the Golgi proteases involved in the release of SREBP, controlling the transcription of lipid metabolism regulating genes ; mitochondrial proteases involved in the importation and further maturation of nuclear genome encoded proteins ; proteasome regulating the transcription of several genes through NF-B ; P450 cytochromes. Nucleosides inhibitors of the viral reverse transcriptase exhibit nuclear and mitochondrial DNA toxicity, disrupt lipid and protein glycosylation and inhibit telomerase. Therefore antiretroviral therapies target several pathways involved in accelerated or normal aging. Their combined effects are added to viral infection direct symptoms or to cell abnormalities induced by viral proteins.
Our multicentric (the 3 CISIH from Marseille, Nice and Montpellier) 3 year- long study will analyse 50 HIV1-infected naive patients (A group), apparied to 50 age- and sex-matched seronegative control subjects (recruited by CIC-UPCET of Marseille) and 100 HIV1-infected patients in first line of antiretroviral therapy for at least 12 months (B group). Patients of group A and B will be recruited in the 3 clinical unit. The HIV1- infected patients will be evaluated four times, at baseline, then every 12 months during 3 years. In case of initiation or changing of antiretroviral therapy, patients will be evaluated once more. Control subjects will be only evaluated at baseline.
Peripheral blood biological tests will be the following [Laboratory designation] : i/ viral load measurement, PBMC isolation, DNA extraction, proviral DNA measurement, cell and DNA storage [Virology, Timone CHU, Marseille]; ii/ assays of CD4, CD8, glycemia, insulinemia, HOMA, total-, LDL- and HDL-cholesterol, triglycerides [Biochemistry labs from the 3 CHU] ; iii/ antiretroviral drug assay (mass spectrometry) [Pharmacokinetics, Timone CHU, Marseille]; iv/ detection (western blotting, immunocytochemistry combined to image analysis of nuclear abnormalities) of PBMC nuclear, cytosolic and mitochondrial targets of antiretroviral drugs : A and B lamins, NF-B + I-B and proteasome activity assay, CD36 (glycosylation), mitochondrial Hsp70, ROS mitochondrial production, mitochondrial inner membrane potential, cytochrome C oxidase subunits 2 and 4 [Cell Biology, Timone CHU, Marseille] ; v/ genotyping the antiretroviral targets : lamin A (ZMPSTE24) and B (Rce1) processing proteases, Golgi SREBP-releasing proteases (MBTPS1 and S2), mitochondrial deoxynucleoside transporters (SLC25A4 to A6), mitochondrial proteases (MPPA, paraplegin) involved in processing of nuclear encoded proteins during their mitochondrial import ; quantitative PCR measurement of telomere length [Molecular Genetics, Timone CHU, Marseille]. Marseille's CIC-UPCET collaborated to the protocol design, will recruit control subjects and will be responsible for statistical treatment of data.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A HIV1-infected naive patients | – | Biological: Peripheral blood biological tests |
| B HIV1-infected patients | – | Biological: Peripheral blood biological testsin 1st line of ARV therapy for at least 12 months |
| C= control Non infected HIV volunters | – | Biological: Peripheral blood biological tests |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 50 HIV1-infected naive patients (A group), apparied to 50 age- and sex-matched seronegative control (C group) subjects and 100 HIV1-infected patients in first line of antiretroviral therapy for at least 12 months (B group)
Key inclusion criteria (4 listed)
- Age ≥ 18 years and <65 years Able to give written consent Covered by French Social Security Non infected by HIV-2
- - A group HIV1-infected naive patients
- -B group infected patients in first line of antiretroviral therapy for at least 12 months
- -C group HIV seronegative Confirmed by a fast test of screening of the HIV at day one of study
Key exclusion criteria (6 listed)
- Age < 18 years and > 65 years
- Not Able to give written consent
- Not Covered by French Social Security
- Infected by HIV-2
- treated by statin or biphosphonat amino
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 |
|---|---|---|
| Peripheral blood biological testsA group and B group will be evaluated three times, at baseline, then every 12 months during 3 years. In case of initiation or changing of antiretroviral therapy, patients will be evaluated once more. Control subjects will be only evaluated at baseline. | Biological | A HIV1-infected naive patients, B HIV1-infected patients, C= control Non infected HIV volunters |
Primary outcome
lamin A measurement by western blotting
1 secondary outcome
Peripheral blood biological tests (cellular, molecular genetic)
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 27 Dec 2012.
- Derived from this study: PubMed 23285253Perrin S, Cremer J, Faucher O, Reynes J, Dellamonica P, Micallef J, Solas C, Lacarelle B, Stretti C, Kaspi E, Robaglia-Schlupp A, Nicolino-Brunet C, Tamalet C, Levy N, Poizot-Martin I, Cau P, Roll P. HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. PLoS One. 2012;7(12):e53035. doi: 10.1371/journal.pone.0053035. Epub 2012 Dec 28.
- Derived from this study: PubMed 22829920Perrin S, Cremer J, Roll P, Faucher O, Menard A, Reynes J, Dellamonica P, Naqvi A, Micallef J, Jouve E, Tamalet C, Solas C, Pissier C, Arnoux I, Nicolino-Brunet C, Espinosa L, Levy N, Kaspi E, Robaglia-Schlupp A, Poizot-Martin I, Cau P. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 "Aging" study. PLoS One. 2012;7(7):e41129. doi: 10.1371/journal.pone.0041129. Epub 2012 Jul 19.
- Related InfoLink provided by the sponsor.
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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.
Isabelle POIZOT-MARTIN principal investigator
CHU Sainte Marguerite -Marseille
Marie-Pierre DROGOUL principal investigator
CHU Sainte Marguerite -Marseille
Olivia FAUCHER principal investigator
CHU Sainte Marguerite -Marseille
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 Infection and Aging Accelerated, run by French National Agency for Research on AIDS and Viral Hepatitis 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 4 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 27 Dec 2012. 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?
lamin A measurement by western blotting. 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 NCT01038999, 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 27 Dec 2012.