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Sponsored by: |
Assistance Publique - Hôpitaux de Paris |
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Information provided by: | Assistance Publique - Hôpitaux de Paris |
ClinicalTrials.gov Identifier: | NCT00702013 |
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.
Condition |
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HIV Infections |
Study Type: | Observational |
Study Design: | Cross-Sectional |
Official Title: | Ontogenesis of the P-Glycoprotein in Human Lymphocytes: Influence of the Human Immunodeficiency Virus (HIV) and Antiretroviral Therapeutics |
blood sample for DNA extraction and genetic polymorphism of Mdr1
Estimated Enrollment: | 310 |
Study Start Date: | March 2007 |
Estimated Study Completion Date: | June 2009 |
Estimated Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
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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.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
HIV Patients children and adults and controls
Inclusion Criteria:
Exclusion Criteria:
Contact: Jean-Marc Tréluyer, MD, PhD | 33-15-841-2885 | jm.treluyer@svp.aphp.fr |
France | |
Hopital Necker Enfants Malades | Recruiting |
Paris, France, 75015 | |
Contact: Jean-Marc Tréluyer, MD, PhD 33-15-841-2885 jm.treluyer@svp.aphp.fr | |
Principal Investigator: Stephane Blanche, MD, PhD |
Study Director: | Jean-Marc Tréluyer, MD, PhD | AP-HP |
Responsible Party: | Department Clinical Research of Developpement ( Yannick Vacher ) |
Study ID Numbers: | P070102 |
Study First Received: | June 18, 2008 |
Last Updated: | July 1, 2008 |
ClinicalTrials.gov Identifier: | NCT00702013 |
Health Authority: | France: Ministry of Health |
P-glycoprotein lymphocyte HIV children ontogenesis |
Ontogenesis P-gp in human lymphocytes Study of the influence of HIV infection Antiretroviral treatments on P-gp activity Expression in human lymphocytes |
Virus Diseases Sexually Transmitted Diseases, Viral HIV Infections Interferons Sexually Transmitted Diseases |
Acquired Immunodeficiency Syndrome PS-K Retroviridae Infections Immunologic Deficiency Syndromes |
Interferon Inducers Anti-Infective Agents Radiation-Protective Agents RNA Virus Infections Slow Virus Diseases Immune System Diseases Immunologic Factors Antineoplastic Agents Physiological Effects of Drugs |
Adjuvants, Immunologic Infection Antibiotics, Antineoplastic Protective Agents Antiviral Agents Pharmacologic Actions Therapeutic Uses Lentivirus Infections |