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.

摘要：临床核心的目的是招募和表征海地的患者同伙，并收集和 在项目1-3中进行结核病研究（TB）持久性研究的临床样本。将进行核心活动 由Haitien d'Etude du sarcome de Kaposi et des Instrections机会主义者（GHESKIO）组成 海地王子。格斯基奥（Gheskio）是一个海地非营利组织，成立于1982年，致力于 研究，服务和艾滋病毒和结核病的培训。它已经进行了NIH支持38的临床研究 多年，并且具有进行拟议的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，大量结核病患者人群，BSL-3 TB实验室，A 数据管理中心和机构审查委员会。 2019年，格斯基奥（Gheskio）诊断并治疗了1,456 培养患者证实了结核病，其中包括225名结核病的重新治疗患者，15个家庭 有多个兄弟姐妹的结核病和321例HIV阴性患者患有肺腔疾病和高痰液 结核病治疗完成后有高风险的细菌负荷。这个Tri-i的主要重点 TBR正在治疗后持续感染（PTPI）和TB复发。鉴于超过100万 2018年，世界上诊断出的1000万例结核病病例是经常性结核病病例，了解遗传，免疫学 TB持久性和复发的药代动力学相关性至关重要。 Tri-I TBRU临床核心的特定目标是： 1）对250例复发性结核病，250个HIV阴性患者进行横断面研究 具有单一发作的结核病对照，在多个兄弟姐妹中有50个具有活性结核病的家庭。控制 结核病和治疗后随访的一集将与年龄，性别和时间的复发案例相匹配 自完成第一结核病方案以来。将有一次学习访问。包括整体在内的临床样本 宿主DNA和RNA，血清，PBMC，尿液和粪便的血液将运送到纽约。 2）对500名HIV阴性药物敏感的结核病患者进行纵向队列研究 胸部X光片上的空腔，高痰液杆菌载荷和复发性结核病的高风险。参与者 将入学抗结核治疗（2HRZE/4HR），然后在24个月后进行 完成治疗（总计30个月）。我们估计有40-50名参与者将发展复发性结核（4-- 5次复发/100例患者年）。结核分离株将进行基因分型，以确定复发是否为 从先前感染的缓解（估计占病例的85％）或重新感染了新菌株（15％）。我们将量化 M.使用BACTEC的时间 - 积极性。我们将收集包括血液，PBMC，尿液和粪便在内的样本，第2、4、8周 治疗完成后3个月和6个月的治疗完成，以通过TBRU项目1-3和PIP核心进行分析。