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Ontogenesis of the P-Glycoprotein in Human Lymphocytes Influence of HIV and Antiretroviral Therapeutics (Onto-Pgp)

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00702013
First received: June 18, 2008
Last updated: November 10, 2010
Last verified: October 2010

June 18, 2008
November 10, 2010
March 2007
March 2009   (final data collection date for primary outcome measure)
The activity and expression of P-glycoprotein at the time when the blood sample was taken. [ Time Frame: immediately ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00702013 on ClinicalTrials.gov Archive Site
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Ontogenesis of the P-Glycoprotein in Human Lymphocytes Influence of HIV and Antiretroviral Therapeutics
Ontogenesis of the P-glycoprotein in Human Lymphocytes: Influence of the Human Immunodeficiency Virus (HIV) and Antiretroviral Therapeutics

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 transporter's 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.

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 transporter's 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 and/or 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.

Observational
Time Perspective: Cross-Sectional
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Retention:   Samples With DNA
Description:

blood sample for DNA extraction and genetic polymorphism of Mdr1

Non-Probability Sample

HIV Patients children and adults and controls

HIV Infections
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
310
August 2009
March 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age, HIV status

Exclusion Criteria:

  • None
Both
Not Provided
Yes
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00702013
P070102
No
Yannick Vacher, Department Clinical Research of Developpement
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: Jean-Marc Tréluyer, MD, PhD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP