Clinical trial NCT00730678: Pharmacogenetic Determinants Of Treatment Response In Children
Official title: Pharmacogenetic Determinants Of Treatment Response In Children
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: All Malignancies
Children Being Treated for Catastrophic Illness
Keywords: Metabolism
Pharmacogenetic testing
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2008-08-08
Enrollment: 8800
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients treated at St. Jude Children's Research Hospital are eligible to participate in this study.

Brief summary: To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates. To investigate the nature of heritability and the genetic basis of pharmacogenetic traits by studying family members of individuals with specific genotypes.

Detailed description: Pharmacogenetics is that discipline devoted to elucidating the genetic determinants of drug response. Particularly in the area of drug metabolism, many genes exhibit genetic polymorphism; that is, a stable percentage of the population (which generally differs by ethnic group) is deficient in the functional expression of the enzyme involved, and the deficiency is typically inherited as an autosomal recessive trait. With currently known polymorphisms in drug metabolism, the percentage of homozygous deficient individuals ranges from 0.3% to as many as 90% of the population, depending on the enzyme and the ethnic group.

Our prior studies have revealed multigenic pharmacogenetic models that are significantly predictive of various drug response phenotypes (e.g., drug resistance, drug clearance, drug toxicity, disease response) in children with ALL. The large number of candidate loci and the relatively small number of patients illustrate the fact that larger sample sizes are required to definitively establish these polygenic models. The fact that there were significant race/genotype interactions, such that predictions differed in whites vs blacks, highlights the need for adequate numbers of patients within racial and ethnic groups to allow differential analysis of genotypic predictors after adjusting for confounding demographic factors in pharmacogenetic studies via stratified design and analyses.

Eligibility criteria: Inclusion Criteria:

* Any patients under evaluation/treatment at St. Jude Children's Research Hospital (SJCRH)
* Parents or family members of St. Jude patients
* Non patient volunteers
* All study subjects must provide informed consent for participation
* Assent/Consent of the patient (parent) must be provided prior to attempts made by investigators to enroll a family member of a SJCRH patient

Exclusion Criteria:

Primary outcomes:
measure: To investigate whether genetic polymorphisms in genes encoding proteins involved in the metabolism or effects of drugs or environmental agents influence the disposition or effects of these xenobiotic substrates.
timeFrame: 28 years
Secondary outcomes:
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Clinton F. Stewart, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: