Ignite Creation Date:
2024-05-06 @ 1:42 AM
Last Modification Date:
2024-10-26 @ 11:08 AM
Study NCT ID:
NCT01874743
Status:
UNKNOWN
Last Update Posted:
2013-06-12
First Post:
2012-12-26
Brief Title:
Rosuvastatin to Decrease Residual Immune Activation in HIV Infection
Sponsor:
Institut de Médecine et dEpidémiologie Appliquée - Fondation Internationale Léon MBa
Organization:
Institut de Médecine et dEpidémiologie Appliquée - Fondation Internationale Léon MBa
Study Overview
Official Title:
Pilot Study of the Impact of Rosuvastatin Administration on Residual Chronic Immune Activation Under Antiretroviral Therapy CESAR Crestor En Sus Des AntiRétroviraux
Status:
UNKNOWN
Status Verified Date:
2012-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CESAR
Brief Summary:
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 20mgday 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 CD4CD8 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 CD4CD8 T-cell ratio To evaluate the tolerance of Rosuvastatin at the dose of 20 mgday
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 plasmaserum 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 CD4CD8 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 CD4CD8 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 copiesmL
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 500mm3
No indication for a treatment with statins LDL cholesterol 41 mmolL under stable diet
Non-inclusion criteria
Patients receiving Maraviroc
Patients receiving immune suppressing drugs
Ongoing opportunistic bacterial or viral infection
CRP 10 mgmL
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 mmolL
DFG 60 mL min173 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 mgd 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 005
Substudies
Estimated planning or Study Trial timetable Trialstudy start date April 2012 Enrolment period 12 months Subject participation duration 6 months Total trialstudy duration 18 months Estimated studytrial 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
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 plasmaserum 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 CD4CD8 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 CD4CD8 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 copiesmL
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 500mm3
No indication for a treatment with statins LDL cholesterol 41 mmolL under stable diet
Non-inclusion criteria
Patients receiving Maraviroc
Patients receiving immune suppressing drugs
Ongoing opportunistic bacterial or viral infection
CRP 10 mgmL
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 mmolL
DFG 60 mL min173 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 mgd 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 005
Substudies
Estimated planning or Study Trial timetable Trialstudy start date April 2012 Enrolment period 12 months Subject participation duration 6 months Total trialstudy duration 18 months Estimated studytrial 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None