Estudo da história natural para determinar o fenótipo do metabolismo de drogas e o DNA de fonte de linha germinativa apropriada em pacientes submetidos ao transplante de células -tronco hematopoiéticas alogênicas
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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Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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:
- Age >=18 years
- Must be 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. Liver biopsies will be collected from participants undergoing hepatic surgery.
- Whole genome sequencing with Aldy analysis 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.
- Up to 88 participants will be enrolled.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Ashley E Carpenter
- Número de telefone: (240) 760-6009
- E-mail: carpentera@mail.nih.gov
Estude backup de contato
- Nome: Christopher G Kanakry, M.D.
- Número de telefone: (240) 760-6171
- E-mail: christopher.kanakry@nih.gov
Locais de estudo
-
-
Maryland
-
Bethesda, Maryland, Estados Unidos, 20892
- Recrutamento
- National Institutes of Health Clinical Center
-
Contato:
- NIH Clinical Center Office of Patient Recruitment (OPR)
- Número de telefone: TTY dial 711 800-411-1222
- E-mail: ccopr@nih.gov
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Método de amostragem
População do estudo
Any gender, any age greater than or equal to 18 years, who will donate or receive an allogeneic HSCT.
Descrição
- 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.
EXCLUSION CRITERIA:
- 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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Modelos de observação: COHORT
- Perspectivas de Tempo: PROSPECTIVE
Coortes e Intervenções
Grupo / Coorte |
Intervenção / Tratamento |
|---|---|
|
Cohort 1
Participants undergoing allogeneic HSCT and donors |
Short tandem repeat (STR) analysis from genomic DNA extracted from biospecimens. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic hematopoietic stem cell transplant (HSCT)
Prazo: 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. |
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.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Christopher G Kanakry, M.D., National Cancer Institute (NCI)
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 10001796
- 001796-C
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
Prazo de Compartilhamento de IPD
Data will be shared after completion of the primary endpoint per the data management sharing plan.
Critérios de acesso de compartilhamento IPD
Data may be requested by contacting the Principal Investigator.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
- CIF
Informações sobre medicamentos e dispositivos, documentos de estudo
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