Trial record 3 of 39 for:    " June 18, 2008":" July 18, 2008"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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
  Purpose

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
HIV Infections

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Ontogenesis of the P-glycoprotein in Human Lymphocytes: Influence of the Human Immunodeficiency Virus (HIV) and Antiretroviral Therapeutics

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • The activity and expression of P-glycoprotein at the time when the blood sample was taken. [ Time Frame: immediately ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood sample for DNA extraction and genetic polymorphism of Mdr1


Enrollment: 310
Study Start Date: March 2007
Study Completion Date: August 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
2
3
4
5
6
7
8

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 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

HIV Patients children and adults and controls

Criteria

Inclusion Criteria:

  • age, HIV status

Exclusion Criteria:

  • None
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00702013

Locations
France
Hopital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean-Marc Tréluyer, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Yannick Vacher, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier: NCT00702013     History of Changes
Other Study ID Numbers: P070102
Study First Received: June 18, 2008
Last Updated: November 10, 2010
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Krestin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents

ClinicalTrials.gov processed this record on August 21, 2014