Ignite Creation Date:
2024-05-05 @ 7:37 PM
Last Modification Date:
2024-10-26 @ 9:51 AM
Study NCT ID:
NCT00702013
Status:
COMPLETED
Last Update Posted:
2010-11-11
First Post:
2008-06-18
Brief Title:
Ontogenesis of the P-Glycoprotein in Human Lymphocytes Influence of HIV and Antiretroviral Therapeutics
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Ontogenesis of the P-glycoprotein in Human Lymphocytes Influence of the Human Immunodeficiency Virus HIV and Antiretroviral Therapeutics
Status:
COMPLETED
Status Verified Date:
2010-10
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:
Onto-Pgp
Brief Summary:
The P-glycoprotein P-gp is a membranous transporter that modulates the intracellular concentrations of many drugs and plays thus a major role in the efficacy of the therapeutics that act within the lymphocytes such as antiretroviral drugs We aim at studying the evolution of this transporters expression and activity on lymphocytes in relation with the human development from newborns to adults We also aim at studying the influence of HIV and antiretroviral treatments on this transporter especially anti-protease drugs within the children population
Detailed Description:
Several groups of drugs involved in the treatment of major pathologies act within the lymphocyte such as anticancer immunosuppressive and antiretroviral drugs These molecules depend on membranous transporters to get inside the lymphocyte and be effective Among those transporters the P-glycoprotein P-gp plays a major role especially because of the variety of its substrates among therapeutic molecules Its expression and activity are well known within the adult population as well as its modulations mediated by certain groups of drugs such as protease inhibitors in the treatment of HIV Yet there is very little data on children even though they are exposed to the same therapeutic molecules as the adults Therefore we aim at studying the evolution of this transporters expression and activity on the different lymphocyte populations in relation to the human development from newborns to adults We also aim at studying the influence of HIV and antiretroviral treatments on this transporter especially anti-protease drugs within the children population P-gp activity is quantified by flow cytometry through the efflux of a fluorescent substrate in the presence or absence of a P-gp inhibitor P-gp expression is measured on isolated motonucleus cells with the quantification of mRNA encoded for the transporter by RT-PCR Reverse Transcription - Polymerase Chain Reaction Patients of every age from newborns to adults are recruited within eight different age groups and three HIV status groups HIV non infected HIV infected untreated HIV infected treated The objective is to recruit ten patients in each age group for each HIV status Blood samples are obtained from hospitalized children and adults with their consent The patients will be recruited for one year Our objective is to determine whether the P-gp expression andor activity are influenced by age HIV status and antiretroviral treatments in order to prevent depending on developmental stages ineffectiveness or toxicity due to inadequate intracellular concentrations
After the first evaluations principal investigators decided to add one year more for three groups on eight
For two groups of these three genetic polymorphism of Mdr1 will be done
After the first evaluations principal investigators decided to add one year more for three groups on eight
For two groups of these three genetic polymorphism of Mdr1 will be done
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