Precision Diagnostics in Inflammatory Bowel Disease, Cellular Therapy and Transplantation (The PREDICT Trial)
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 1,000
- 试验地点
- 4
- 主要终点
- Perform flow cytometry, TCR deep sequencing and whole transcriptome analysis on T cells purified from GI endoscopy samples taken for presumed GI GVHD, inflammatory bowel disease (IBD), and functional gastrointestinal disease (FGID).
研究概览
简要总结
The goal of the Precision Diagnosis in Inflammatory Bowel Disease, Cellular Therapies, and Transplantation (PREDICT) trial is to apply a systems-biology approach to enable precision diagnostics for the key immunologic outcomes for patients with Inflammatory Bowel Disease, Cellular Therapeutics and Transplantation. This approach will deepen the understanding of the molecular mechanisms driving auto- and allo-immune diseases and serve as a critical platform upon which to design evidence-based treatment paradigms for these patients.
This research study will examine the immunology of auto- and allo-immune gastrointestinal disturbances such as Inflammatory Bowel Disease (IBD), Graft-versus-Host Disease (GVHD), and Functional Gastrointestinal Disorder (FGID), as well as the immune manifestations after CAR-T and other cellular therapeutics. The Investigators seek to use blood and tissue samples in order to better understand the mechanisms driving these diseases and their therapies.
The Investigators further hypothesize that longitudinal systems-based immunologic analysis will enable the patient-specific determination of the molecular evolution of IBD, GVHD and the response to cellular therapeutics, as well post-transplant defects in protective immunity, and determine which pathways, when perturbed, can cause clinical disease. The discovery of these pathways will lead to improved diagnostic, prognostic and treatment approaches, and to personalized therapeutic decision-making for these patients.
详细描述
Hypotheses:
Hypothesis #1: The Investigators hypothesize that they can define the molecular mechanisms responsible for Inflammatory Bowel Disease (IBD) and gastrointestinal (GI) acute GVHD and differentiate it from other inflammatory disorders by using advanced immunologic analysis including flow cytometry, TCR deep sequencing and transcriptomics.
Hypothesis #2: The Investigators further hypothesize that longitudinal systems-based immunologic analysis will enable the patient-specific determination of the molecular evolution of IBD as well as acute and chronic GVHD as well post-transplant defects in protective immunity, and determine which pathways, when perturbed, can cause clinical disease. The discovery of these pathways will lead to improved diagnostic, prognostic and treatment approaches, and to personalized therapeutic decision-making for patients undergoing hematopoietic stem cell transplantation (HCT).
Hypothesis #3: We hypothesize that we can define the molecular mechanisms, phenotypic and functional immunologic characteristics involved in distinct determinants of adoptive cellular therapies, including the efficacy, longevity and toxicity associated with cellular therapy. Longitudinal characterization of cellular therapeutics and the endogenous immune response they elicit using advanced immunologic analysis including flow cytometry, mass spectrometry, TCR deep sequencing and single-cell transcriptomics will allow identification and distinction of pathways critical for efficacy and toxicity and enable subsequent therapeutic modulation.
Hypothesis #4: We hypothesize that differences in the gut microbiome of patients with IBD and recipients of HCT play a major role in disease severity and overall clinical outcomes in both diseases (e.g. bacteremia, unexplained fevers, mortality). The longitudinal characterization of the gut microbial communities by next generation sequencing will allow for detection of sequential microbial changes that coincide with observed clinical changes. the discovery of significant changes in the microbiome that are repeatedly observed with a particular clinical outcome will lead to better mechanistic understanding of its pathophysiology and inform future diagnostic and preventive approaches.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for HCT patients:
- •Patients must be at least 1 month old and weigh >/= 3 kg.
- •Patients receiving any allogeneic or autologous hematopoietic stem cell transplantation (bone marrow, peripheral blood, or cord blood transplant).
- •Patients and/or parents or legal guardians must sign a written informed consent.
- •B. Inclusion Criteria for Adoptive Cellular Therapy (CT) patients:
- •Weight ≥3 kg
- •Patients receiving adoptive cellular therapy
- •Patient and/or legal guardian must sign written informed consent
- •C. Inclusion criteria for Healthy Donor Blood volunteers:
- •Participant does not have signs/symptoms of present illness
- •Participant does not have a known disease affecting the immune system
- •Participant is not on any medication/s that suppress immune system
- •Obtain informed consent
- •D. Inclusion criteria for HCT Related and Unrelated Donors:
- •Age >1 years of age
- •Weight >3 kg
- •Obtain informed consent
- •E. Inclusion criteria for IBD & FGID patients:
- •Patients must be at least 6 years old and weigh >/= 10 kg.
- •Patients being evaluated for IBD (new diagnosis or follow up of established disease), OR
- •Patients being evaluated for FGID (new diagnosis or follow up of established disease).
- •Obtain informed consent
- •F. Inclusion criteria for HCT & Cell Therapy Household Members:
- •Household member of a patient who is receiving HCT or Cell Therapy and who is participating in the PREDICT study
- •Age >1 years of age
- •Weight >3 kg
- •Obtain informed consent
排除标准
- 未提供
结局指标
主要结局
Perform flow cytometry, TCR deep sequencing and whole transcriptome analysis on T cells purified from GI endoscopy samples taken for presumed GI GVHD, inflammatory bowel disease (IBD), and functional gastrointestinal disease (FGID).
时间窗: 1 year
To identify the mechanisms specific for auto-immune and allo-immune GI disorders.
Perform flow cytometry, TCR deep sequencing and transcriptome analysis on T cells from the peripheral blood in patients diagnosed with GI GVHD, IBD and FGID and patients receiving cellular therapies.
时间窗: 1 year
To identify the mechanisms specific for allo- and auto-immune diseases and the consequences of cellular therapy delivery.
次要结局
- Perform microbiome analysis longitudinally in patients with auto- and allo-immune diseases.(1 year)
- Perform longitudinal immune analysis on T- and B-cells as well as measurements of serum antibody titers from patients with allo- and auto-immune disorders who receive immunization against COVID-19.(1 year)
- Perform longitudinal immune analysis on T cells and B cells purified from patients with allo- and auto-immune diseases and those receiving cellular immunotherapies.(1 year)
研究者
Leslie Kean
MD, PhD
Boston Children's Hospital