Ignite Creation Date:
2024-05-05 @ 9:36 PM
Last Modification Date:
2024-10-26 @ 10:07 AM
Study NCT ID:
NCT00925756
Status:
COMPLETED
Last Update Posted:
2020-08-19
First Post:
2009-06-18
Brief Title:
CCR5 Inhibitor Treatment Intensification on CD4 T-cell Recovery
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
The Impact of CCR5 Inhibitor Treatment Intensification on CD4 T-cell Recovery and Gene Expression Profiles in HIV-Infected Patients With Viral Suppression
Status:
COMPLETED
Status Verified Date:
2020-08
Last Known Status:
None
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:
None
Brief Summary:
CCTG 590 is a open-label study to evaluate the impact of therapy intensification with Maraviroc MVC a CCR5 inhibitor to a stable suppressive HIV antiretroviral regimen on the rate of CD4 T-cell recovery and gene expression profiles Patients on a stable first-line HIV regimen with continued viral suppression and sub-optimal CD4 T-cell counts will be eligible for this study Those who are found to be eligible will have MVC dose-adjusted to background HIV regimen added to their current HIV regimen for 24 weeks After the 24 week intensification the MVC will be discontinued the original antiretroviral regimen will be continued and the subjects will be followed for an additional 12 weeks
The investigators hypothesize that MVC will improve the rate of CD4 recovery This improved CD4 recovery will be associated with favorable changes in gene expression profiles of genes involved with CD4 maintenance and circulation
The investigators hypothesize that MVC will improve the rate of CD4 recovery This improved CD4 recovery will be associated with favorable changes in gene expression profiles of genes involved with CD4 maintenance and circulation
Detailed Description:
Blunted CD4 T-cell responses during viral control may be a consequence of on-going T-cell destruction in the regenerative phase of CD4 recovery from activation-induced apoptosis andor reduced production from decreased thymic output Maraviroc a CCR5 inhibitor may improve the clinical status of HIV-infected by two distinct mechanisms First by blocking HIV entry into CD4 T-cells CCR5 inhibitors have direct antiviral activity Second as the pro-inflammatory state of HIV infection up-regulates CCR5 ligands and receptors this CCR5 receptor antagonist may abrogate immune activation and resultant T-cell apoptosis Importantly MVC binds CCR5 receptors without inducing intracellular signaling or altering cell-surface expression Potentially MVC intensification during viral suppression with ART may further decrease persistent activation-induced apoptosis and improve repair and remodeling of lymphoid tissue leading to increased CD4 T-cell recovery and function
The aim of this study is to evaluate a potentially therapeutic immunomodulatory effect of MVC Several measures of immune homeostasis will be determined in this study including functional genomic analysis and extended T-cell phenotyping Genes responsive to MVC therapy will be identified and categorized into functional groups Based upon existing literature of the identified genes and observed immune responses change in CD4CD8 subsets during MVC therapy a model of CCR5 responsive-genes and potential impact on immune recovery will be outlined Potentially individuals experiencing immune discordance during suppressive ART may be better treated by MVC antiretroviral intensification
1 We hypothesize that expression will decrease among genes involved in immune activation NF-kB MAPK nuclear factor of activated T-cells MYD88 and STAT1 apoptosis Fas ligand and TRAIL and traffickingrepopulation of T-cells CCR5 MIP-1α MIP-1β and RANTES and increase among genes involved in tissue repair platelet-derived growth factor insulin-like growth proteins and osteoblast-specific transcription factor
1 The gene expression profiles induced by MVC will be associated with a favorable increase in the rate of CD4 T-cell recovery
2 The rate of CD4 recovery cellsmonth will be greater during MVC compared to before
3 The proportion of cells expressing activation apoptosis markers will decrease from baseline and this decrease will be associated with improved CD4 recovery
4 The proportion of naïve cells will increase from baseline and this increase will be associated with improved CD4 recovery
5 The rate of CD4 recovery will be greater among those subjects receiving PI-containing treatment regimens compared to those receiving NNRTI-containing treatment regimen
The aim of this study is to evaluate a potentially therapeutic immunomodulatory effect of MVC Several measures of immune homeostasis will be determined in this study including functional genomic analysis and extended T-cell phenotyping Genes responsive to MVC therapy will be identified and categorized into functional groups Based upon existing literature of the identified genes and observed immune responses change in CD4CD8 subsets during MVC therapy a model of CCR5 responsive-genes and potential impact on immune recovery will be outlined Potentially individuals experiencing immune discordance during suppressive ART may be better treated by MVC antiretroviral intensification
1 We hypothesize that expression will decrease among genes involved in immune activation NF-kB MAPK nuclear factor of activated T-cells MYD88 and STAT1 apoptosis Fas ligand and TRAIL and traffickingrepopulation of T-cells CCR5 MIP-1α MIP-1β and RANTES and increase among genes involved in tissue repair platelet-derived growth factor insulin-like growth proteins and osteoblast-specific transcription factor
1 The gene expression profiles induced by MVC will be associated with a favorable increase in the rate of CD4 T-cell recovery
2 The rate of CD4 recovery cellsmonth will be greater during MVC compared to before
3 The proportion of cells expressing activation apoptosis markers will decrease from baseline and this decrease will be associated with improved CD4 recovery
4 The proportion of naïve cells will increase from baseline and this increase will be associated with improved CD4 recovery
5 The rate of CD4 recovery will be greater among those subjects receiving PI-containing treatment regimens compared to those receiving NNRTI-containing treatment regimen
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