N-PhenoGENICS: Neurocognitive-Phenome, Genome, Epigenome and Nutriome In Childhood Leukemia Survivors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- DIVERGET
研究概览
简要总结
To find possible therapeutic targets to help prevent long-term brain and behavioural side effects in survivors of childhood leukemia that may have been caused by chemotherapy (Treatment-Related late Adverse Neuro-Cognitive Effects: TRANCE). The study hypothesis is that genetic variations of the elements in the folate-related cycles and methotrexate disposition networks are associated with the deficit phenotype (TRANCE) of childhood leukemia survivors.
详细描述
Hypothesis Genetic variants of the elements in the folate-related cycles and methotrexate disposition networks are associated with the TRANCE phenotype of childhood leukemia survivors.
Objectives
- To identify TRANCE phenotypes of the childhood leukemia survivors.
- To characterize the folate and vitamin B12 levels of these children
- To identify DNA methylation patterns associated with TRANCE trait in the leukemia survivors
- To identify SNPs associated with the TRANCE trait in the leukemia survivors.
- To identify the "deficit genotype" associated only with the TRANCE leukemia survivors, but not with general population children who show developmental phenotypes similar to TRANCE: TRANCE-unique deficit variant
- To replicate the association between the TRANCE-unique deficit variants and the TRANCE trait in a population of childhood leukemia survivors.
- To evaluate the importance of rare genetic variants in the TRANCE trait in the leukemia survivors.
Study design: A case-control study of leukemia survivors
Analyses
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 8 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Past diagnosis of acute lymphoblastic leukemia
- •8 years : 0 months - 20 years : 11 months old at the time of their study visit
- •At least 2 years : 0 months from the last treatment for acute lymphoblastic leukemia at the time of their study visit
- •Continuous complete remission and undergone no bone marrow transplantation or cranial radiation therapy
- •Fluent in English (a subject and one parent) for test completion
- •Signed informed consent
排除标准
- •Inability to complete the phenotyping tests
- •Down Syndrome diagnosis
结局指标
主要结局
DIVERGET
时间窗: Within 6 months from the enrolment
This is a short battery of tests that has been shown to be predictive of both global and academic impairment in survivors of childhood cancer. All neuro-cognitive tests are done on a same day.
Stop Signal Task (SST)
时间窗: Within 6 months from the enrolment
Response inhibition, disturbed by behavioral inattention, will be characterized using our task-based computer program, the Stop Signal Task (SST). All neuro-cognitive tests are done on a same day.
CONNERS 3
时间窗: Within 6 months from the enrolment
To characterize behavioural aspects, we will administer the standard measure based on parent report. All neuro-cognitive tests are done on a same day.
Pathway-based gene variant status
时间窗: Within 3 months from the end of enrolment
In the hypothesis-driven genome-wide approach, we will focus on the candidate pathways/regions including (but not limited to): a) Folate/methionine cycle genes and transporters; b) drug metabolizing enzymes and transporters (including families of CYP, SLC and ABC transporters); c) epigenetic modifying factors; and d) neuro-regeneration and tissue repair.
次要结局
- WIAT-III numerical operations and math fluency composite score(Within 6 months from the enrolment)
- Serum vitamin B12(Within 6 months from the enrolment)
- Folate, vitamin B12 and iron intake(Within 6 months from the enrolment)
- Folate status(Within 6 months from the enrolment)
- WISC-IV(Within 6 months from the enrolment)
- Brief Rating Inventory of Executive Function (BRIEF)(Within 6 months from the enrolment)
- N-Back Task(Within 6 months from the enrolment)
- Iron status(Within 6 months from the enrolment)
研究者
Shinya Ito
Division Head, Clinical Pharmacology and Toxicology
The Hospital for Sick Children