Natural History Study to Determine Drug Metabolism Phenotype and Appropriate Germline Source DNA in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)
研究概览
简要总结
Background:
After an allogeneic hematopoietic stem cell transplant (HSCT), the donor genome is found in the recipient s circulation and tissues.
Post-HSCT recipients may receive a medication in which the dosing needs to be adjusted based on genetic variation.
While genes in donor genome may influence dosing and administration of some agents, the majority of established gene-drug pairs in pharmacogenetics are related to expression of metabolic or transporting enzymes located in recipients tissues, often the liver.
Determining which genetic variants influence drug disposition in HSCT recipients is complicated by chimerism in samples that are routinely collected for determining genotype. However, chimerism in tissues is poorly studied in this patient population.
Objectives:
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic HSCT.
Eligibility:
People ages 18 years and older who are enrolled on a clinical trial at the NIH Clinical Center under which they will donate or receive an allogeneic HSCT.
Design:
DNA is collected prior to HSCT and for two years after HSCT.
Blood will be collected and skin fibroblast cell lines will be established prior to HSCT to serve as a reference genome.
Blood, buccal cells, skin, and hair will be monitored for the development of mixed chimerism via detection of short tandem repeats. Liver biopsies will be collected from participants undergoing hepatic surgery.
Pharmacoscan arrays will be conducted to determine which samples are useful for pharmacogenetic testing in participants who receive allogeneic HSCT.
A probe drug cocktail will be administered pre- and post-HSCT to determine if transplantation alters the metabolic phenotype of liver enzymes.
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详细描述
Background:
- After an allogeneic hematopoietic stem cell transplant (HSCT), the donor genome is found in the recipient fs circulation and tissues.
- Post-HSCT recipients may receive a medication in which the dosing needs to be adjusted based on genetic variation.
- While genes in donor genome may influence dosing and administration of some agents, the majority of established gene-drug pairs in pharmacogenetics are related to expression of metabolic or transporting enzymes located in recipients f tissues, often the liver.
- Determining which genetic variants influence drug disposition in HSCT recipients is complicated by chimerism in samples that are routinely collected for determining genotype. However, chimerism in tissues is poorly studied in this patient population.
Primary Objective:
-To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic HSCT.
Eligibility:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA:
- •Age >=18 years
- •Participants must be enrolled on a clinical trial at the NIH Clinical Center (CC) under which they will donate or receive an allogeneic HSCT. The participant and their donor must enroll together to provide a complete set of samples for analysis.
- •Ability of subject to understand and the willingness to sign a written informed consent document.
排除标准
- •Donors are not allowed to enroll without a recipient
- •Prior allogeneic HSCT
- •History of psychiatric disorder which may compromise compliance with protocol requirements.
- •Pregnant and lactating individuals
研究组 & 干预措施
Cohort 1
Participants undergoing allogeneic HSCT and donors
干预措施: Arm 1 (Other)
结局指标
主要结局
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)
时间窗: Pharmacoscan array will be performed within 1 month pre-BM donation in donors and within 1 month pre-HSCT and 12 months post-HSCT in recipients.
Obtaining genotype for analysis of pharmacogene activity by understanding the degree chimerism in commonly utilized diagnostic samples.
次要结局
未报告次要终点