Rosuvastatin to Decrease Residual Immune Activation in HIV Infection (CESAR)

June 11, 2013 updated by: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Pilot Study of the Impact of Rosuvastatin Administration on Residual Chronic Immune Activation Under Antiretroviral Therapy: CESAR (Crestor En Sus Des AntiRétroviraux)

Participating countries: France Objectives Principal objective To evaluate, in HIV-1 infected patients receiving effective antiretroviral therapy, the effect of the addition of Rosuvastatin (dose of 20mg/day) for 3 months, on CD8 T cell activation as assessed by the proportion of peripheral CD8 T cells that co-express the activation markers CD38 and HLA-DR Secondary objectives To evaluate the effect of Rosuvastatin administration on residual CD4 and CD8 T cell activation To evaluate the effect of Rosuvastatin administration on the main serum soluble biomarkers of activation (CRP- HS, D-dimers, IL-6 and soluble CD14) To evaluate the effect of Rosuvastatin administration on CD4 T-cell count and on the CD4/CD8 T-cell ratio To study the relationship between the level of immune activation and the level of residual HIV replication in plasma To study the effect of Rosuvastatin administration on lipid profiles and the correlation between the HDL cholesterol and the CD4/CD8 T-cell ratio To evaluate the tolerance of Rosuvastatin at the dose of 20 mg/day

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Methodology Phase II pilot study; open-label; non comparative, bicentric, on-off design

Estimated enrolment 40 subjects

Outcomes Primary outcome :

• Variation at month 3 in the proportion of CD8 T lymphocytes co-expressing CD38 and HLA-DR

Secondary outcomes :

  • Evolution of plasma/serum levels of CRP-HS, IL-6, soluble CD14 between baseline and month 3 and between month 3 and month 6
  • Evolution of markers of CD4 T-cell activation (HLA-DR, Ki67) and CD8 T-cell activation (CD38, HLA-DR, Ki67) between baseline and month 3 and between month 3 and month 6 and evolution of the CD4/CD8 ratio between baseline and month 3 and between month 3 and month 6
  • Evolution of CD4 T-cell count between baseline and month 3
  • Evolution of HDL and LDL cholesterol between baseline and month 3 and between month 3 and month 6
  • Relationship between HDL cholesterol and CD4/CD8 ratio at baseline, month 3 and month 6
  • Relationship between the levels of T-cell activation and of plasma HIV-RNA levels at a detection level of 3 copies/mL
  • Adverse events grade > 2 Eligibility Inclusion criteria
  • HIV-infected patients receiving a combination of antiretroviral therapy for at least 24 months, unchanged since at least 18 months, exhibiting plasma HIV-RNA level below 20 copies and circulating CD4 T cell count below 500/mm3
  • No indication for a treatment with statins (LDL cholesterol < 4.1 mmol/L under stable diet).

Non-inclusion criteria

  • Patients receiving Maraviroc
  • Patients receiving immune suppressing drugs
  • Ongoing opportunistic, bacterial or viral infection
  • CRP ≥ 10 mg/mL
  • Co-infection with HCV (except if HCV cure), chronic HBV infection with active replication of HBV
  • Indication for a treatment with statins
  • Pregnancy
  • CPK > 3x Normal values
  • ALT or AST > 2x Normal values
  • TG > 4 mmol/L
  • DFG < 60 mL /min/1.73 m2
  • Personal or familial history of genetic muscular disease
  • History of muscular or hepatic toxicity with a statin or a fibrate
  • Liver disease (TP < 70%).
  • Hypothyroidism
  • Concomitant treatment with : Kétoconazole, Itraconazole, Ciclosporine, Erythromycine, Cimétidine, Quinidine, Diltiazem, Vérapamil, systemic corticosteroids, Phénobarbital, Phénytoïne, Carbamazépine, Rifampicine, Lansoprazole
  • Vaccination during the study

Intervention Rosuvastatin (20 mg/d per os) Intervention duration: 3 months Follow-up for 3 additional months

Statistical methods Bilateral Two-sided paired Wilcoxon to analyze the variation in the proportion of CD8 T lymphocytes that co-express CD38 and HLA-DR at month 3 (primary outcome).

The evolution of parameters of interest between 2 visits will also be analyzed using bilateral two-sided paired Wilcoxon test. Statistical significance will be considered for p< 0.05.

Substudies

Estimated planning or Study / Trial timetable Trial/study start date: April 2012 Enrolment period: 12 months Subject participation duration: 6 months Total trial/study duration: 18 months Estimated study/trial completion date: October 2013 [default date: date of last follow-up of last included patient, else justify the chosen date: date of "gel de la base de données", date of end of substudies analyses (think to delay for sampling transport, duration of technical analyses)]

Study / Trial design Phase II open-label pilot bicentric non comparative study. Patients eligible will receive Rosuvastatin for 3 months while continuing antiretroviral therapy. Patients will be followed-up 3 additional months after stopping the study drug (on-off design)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Paris, France, 75015
        • Recruiting
        • HEGP
        • Contact:
        • Principal Investigator:
          • Laurence Weiss, PHD,MD
      • Paris, France, 75012
        • Recruiting
        • St Antoine Hospital
        • Contact:
        • Principal Investigator:
          • Pierre-Marie Girard, PHD,MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV-infected patients receiving a combination of antiretroviral therapy for at least 24 months, unchanged since at least 18 months, exhibiting plasma HIV-RNA level below 20 copies and circulating CD4 T cell count below 500/mm3
  • No indication for a treatment with statins (LDL cholesterol < 4.1 mmol/L under stable diet).

Exclusion Criteria:

  • Patients receiving Maraviroc
  • Patients receiving immune suppressing drugs
  • Ongoing opportunistic, bacterial or viral infection
  • CRP ≥ 10 mg/mL
  • Co-infection with HCV (except if HCV cure), chronic HBV infection with active replication of HBV
  • Indication for a treatment with statins
  • Pregnancy
  • CPK > 3x Normal values
  • ALT or AST > 2x Normal values
  • TG > 4 mmol/L
  • DFG < 60 mL /min/1.73 m2
  • Personal or familial history of genetic muscular disease
  • History of muscular or hepatic toxicity with a statin or a fibrate
  • Liver disease (TP < 70%).
  • Hypothyroidism
  • Concomitant treatment with : Kétoconazole, Itraconazole, Ciclosporine, Erythromycine, Cimétidine, Quinidine, Diltiazem, Vérapamil, systemic corticosteroids, Phénobarbital, Phénytoïne, Carbamazépine, Rifampicine, Lansoprazole
  • Vaccination during the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Rosuvastatine 20 mg
Rosuvastatin 20 mg/day, once a day during 3 months
Drug: Rosuvastatin 20 mg/day
All patients must take 20mg/day of rosavastatin during 3 months
Other Names:
  • Crestor ,(ZD 4522)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CD8 T cell activation
Time Frame: 6 months
To evaluate, in HIV-1 infected patients receiving effective antiretroviral therapy, the effect of the addition of Rosuvastatin (dose of 20mg/day) for 3 months, on CD8 T cell activation as assessed by the proportion of peripheral CD8 T cells that co-express the activation markers CD38 and HLA-DR
6 months
Coexpress activation markers
Time Frame: 6 months
proportion of peripheral CD8 T cells that co-express the activation markers CD38 and HLA-DR
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rosuvastatin administration (on and off)on biomarkers activation
Time Frame: 6 months
• Changes from baseline to month 3 (on rosuvastatin) and from month 3 to month 6 (off rosuvastatin) in levels of CRP-HS, IL-6, soluble CD14 Changes from baseline to month 3 (on rosuvastatin) and from month 3 to month 6 (off rosuvastatin) in the proportion of CD4 T cells expressing HLA-DR or Ki67 activation markers and in the proportion of CD8 T cells expressing HLA-DR and/or CD38 or Ki67 activation marker
6 months
Relationship between the levels of T-cell activation and of plasma HIV-RNA (ultrasensible measure)
Time Frame: 6 months
• Relationship between the levels of T-cell activation and of plasma HIV-RNA levels at a detection level of 3 copies/mL
6 months
CD4 T-cell count and on the CD4/CD8 T-cell ratio
Time Frame: 6 months
  • Changes in CD4 T-cell count between baseline and month 3 •
  • Changes in the CD4/CD8 ratio between baseline and month 3 and between month 3 and month 6
6 months
Lipids profiles on and off rosuvastatine association
Time Frame: 6 months
• Changes from baseline to month 3 (on rosuvastatin) and from month 3 to month 6 (off rosuvastatin) in levels of HDL and LDL cholesterol
6 months
Tolerance of Rosuvastatine
Time Frame: 6 months
To evaluate the tolerance of Rosuvastatin at the dose of 20 mg/day (Number of patients with adverse events grade > 2)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sidaction

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Laurence Weiss, PH,MD, HEGP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2012

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2013

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 26, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 11, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 12, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IMEA 043 CESAR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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