Clinical Core

临床核心

• 批准号: 10430223
• 负责人: Daniel W Fitzgerald
• 金额: $ 41.64万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10430223
• 关键词: Aftercare; Age; Antitubercular Agents; Back; Biological Assay; Blood; Caribbean region; Case Report Form; Center for Translational Science Activities; Chemistry; Chest; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Sciences; Collaborations; Collection; Communities; Computer software; Country; Cross-Sectional Studies; DNA; Data; Data Set; Data Store; Development; Diagnosis; Disease; Drug Kinetics; Drug toxicity; Enrollment; Equipment; Family; Feces; Genetic; Genotype; Genus Mycobacterium; Goals; Government; HIV Seronegativity; HIV/TB; Haiti; Haitian; Hematology; Immunologics; Immunophenotyping; Incidence; Individual; Infection; Institution; Institutional Review Boards; Internet; Laboratories; Laboratory Research; Liquid substance; Longitudinal cohort study; Lung; Microbiology; Molecular; Multi-Drug Resistance; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; New York; Nongovernmental Organizations; Nonprofit Organizations; Outpatients; Participant; Patients; Persons; Plasma; Population; Procedures; Quality Control; RNA; Recurrence; Regimen; Regulation; Relapse; Research; Research Personnel; Research Support; Retreatment; Retrieval; Risk; Sampling; Sampling Studies; Serology; Serum; Services; Shipping; Ships; Siblings; Solid; Sputum; System; Testing; Time; Training; Tuberculosis; Tuberculosis diagnosis; United States National Institutes of Health; Urine; Visit; Whole Blood; chronic infection; cohort; data management; drug sensitivity; drug-sensitive; experience; follow-up; high risk; medical schools; microbiome analysis; monocyte; mortality; mycobacterial; patient population; peripheral blood; programs; recruit; retention rate; screening program; sex; treatment center; tuberculosis treatment; volunteer; welfare

Abstract: The goal of the Clinical Core is to recruit and characterize patient cohorts in Haiti, and to collect and ship clinical samples for studies of tuberculosis (TB) persistence in Projects 1- 3. Core activities will be performed by the Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. GHESKIO is a Haitian non-profit organization which was founded in 1982 and is dedicated to research, service, and training in HIV and tuberculosis. It has conducted NIH supported clinical research for 38 years and has all the essential core components for the conduct of the proposed TBRU studies, including: experienced research staff, out-patient clinics, access to large TB patient populations, a BSL-3 TB laboratory, a data management center, and an institutional review board. In 2019, GHESKIO diagnosed and treated 1,456 patients with culture confirmed TB including 225 re-treatment patients with a second episode of TB, 15 families with multiple siblings with TB, and 321 HIV-negative patients with pulmonary cavity disease and high sputum bacillary load who are at high risk of recurrence after completion of TB treatment. A major focus of this Tri-I TBRU is on post-treatment persistent infection (PTPI) and TB recurrence. Given that more than 1 million of the world’s 10 million cases of TB diagnosed in 2018 were recurrent TB cases, understanding genetic, immunologic and pharmacokinetic correlates for TB persistence and recurrence is critical. The Specific Objectives of the Tri-I TBRU Clinical Core are: 1) Conduct a cross-sectional study of 250 HIV-negative patients with recurrent TB, 250 HIV-negative controls with a single episode of TB, and 50 families with active TB in multiple siblings. Controls with a single episode of TB and post-treatment follow-up will be matched to recurrent cases by age, sex, and time since completion of first TB regimen. There will be a single study visit. Clinical samples including whole blood for host DNA and RNA, serum, PBMCs, urine, and stool will be shipped to New York. 2) Conduct a longitudinal cohort study of 500 HIV-negative drug-sensitive TB patients with pulmonary cavities on chest radiograph, high sputum bacillary load and high risk for recurrent TB. Participants will be enrolled at initiation of anti-tuberculosis therapy (2HRZE/4HR) and followed for 24 months after completion of therapy (30 months total). We estimate that 40 - 50 participants will develop recurrent TB (4- 5 recurrences/100 patient years). M. tuberculosis isolates will be genotyped to determine if recurrence is from relapse of prior infection (estimated 85% of cases) or reinfection with new strain (15%). We will quantify M. tuberculosis in sputum at weeks 1, 2, 3, 4, 8 and 24 weeks during therapy using BACTEC time-to- positivity. We will collect samples including blood, PBMCs, urine, and stool at enrollment, week 2, 4, 8, at the completion of therapy and 3 and 6 months after therapy for analyses by TBRU Projects 1- 3 and PIP Core.

翻译后摘要：临床核心的目标是招募和表征患者队列在海地，并收集和 为项目1- 3中结核病持久性研究运送临床样本。将开展核心活动 由Au港的海地卡波西肉瘤和传染病研究小组（GHESKIO） 海地王子GHESKIO是一个海地非营利组织，成立于1982年，致力于 艾滋病毒和结核病的研究、服务和培训。它已经进行了38年的NIH支持的临床研究 年，并拥有进行拟议TBRU研究的所有基本核心组成部分，包括： 经验丰富的研究人员、门诊诊所、接触大量结核病患者群体、BSL-3结核病实验室、 数据管理中心和机构审查委员会。2019年，GHESKIO诊断和治疗了1，456例 培养确诊结核病患者，包括225例复治结核病患者，15个家庭 321例HIV阴性肺空洞病高痰患者 完成结核病治疗后复发风险高的患者的细菌负荷。本次三一的一个主要焦点是 TBRU是治疗后持续感染（PTPI）和TB复发。鉴于超过100万的 2018年全球确诊的1000万例结核病病例是复发性结核病病例，了解遗传、免疫学、 和药代动力学与结核病持续和复发的相关性是至关重要的。 Tri-I TBRU临床核心的具体目标是： 1)对250例HIV阴性的复发性结核病患者进行横断面研究， 对照组为单次结核病发作，50个家族中有多个兄弟姐妹患有活动性结核病。控件与 单次结核病发作和治疗后随访将按年龄、性别和时间与复发病例相匹配 自从完成第一个结核病治疗方案以来。将进行一次研究访视。临床样本，包括全血 用于检测宿主DNA和RNA的血液、血清、PBMC、尿液和粪便将被运送到纽约。 2)对500例HIV阴性药物敏感性肺结核患者进行纵向队列研究， 胸部X光片上有空洞，痰菌量高，结核病复发的风险高。参与者 将在开始抗结核治疗（2 HRZE/4 HR）时入组，并在治疗后随访24个月 完成治疗（共30个月）。我们估计，40 - 50名参与者将发展为复发性结核病（4- 5例复发/100患者年）。M.将对结核病分离株进行基因分型，以确定是否复发。 既往感染复发（估计85%的病例）或新菌株再感染（15%）。我们将量化 M.在使用BACTEC的治疗期间第1、2、3、4、8和24周痰结核的时间- 积极性我们将在入组时、第2周、第4周、第8周、第10周、第12周和第14周采集样本，包括血液、PBMC、尿液和粪便。 治疗完成后以及治疗后3个月和6个月，通过TBRU项目1- 3和PIP核心进行分析。