2/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial

2/2 强力霉素治疗艾滋病毒感染者肺气肿：DEPTH 试验

• 批准号: 10490292
• 负责人: Catherine A Spino
• 金额: $ 93.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490292
• 关键词: Achievement; Adherence; Adverse event; Age of Onset; Air; Antibiotics; Archives; Biometry; Blood; Budgets; Carbon Monoxide; Carboxyhemoglobin; Case Report Form; Cause of Death; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Collection; Communication; Computer software; Custom; Data; Data Collection; Data Coordinating Center; Data Set; Databases; Diffuse; Disease Progression; Documentation; Doxycycline; Ensure; Esapent; FDA approved; Faculty; Feasibility Studies; Fostering; Funding; General Population; Goals; HIV; Health Status; Hemoglobin; Incidence; Individual; Information Dissemination; Infrastructure; Institutes; Interstitial Lung Diseases; Investigation; Lead; Leadership; Lung diseases; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Medicine; Methodology; Michigan; Monitor; National Heart, Lung, and Blood Institute; Online Systems; Outcome; Oxygen; Participant; Persons; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Pilot Projects; Play; Population; Prevalence; Procedures; Process; Productivity; Protocols documentation; Provider; Pulmonary Emphysema; Pulmonology; Randomized; Recording of previous events; Reporting; Reproducibility; Reproducibility of Results; Research; Research Design; Research Personnel; Risk; Role; Sample Size; Science; Scleroderma; Secure; Services; Slide; Smoking Status; Statistical Data Interpretation; Statistical Methods; Surveys; System; Teleconferences; Testing; Time; TimeLine; Training; United States National Institutes of Health; Universities; Walking; X-Ray Computed Tomography; barometric pressure; base; clinical research site; clinical trial analysis; comorbidity; data management; database design; design; double-blind placebo controlled trial; experience; former smoker; functional status; improved; innovation; lung imaging; meetings; multidisciplinary; operation; patient oriented; primary endpoint; programs; randomized placebo controlled trial; research and development; safety study; safety testing; software development; success; targeted treatment; tool; treatment duration; web site; webinar

The DEPTH trial represents an innovative approach to slowing the progression of emphysema in people living with HIV (PLWH), a population that has accelerated disease progression for which there is no targeted therapy. With our CCC collaborators, we propose a phase II, multi-center, randomized, double-blind, placebo-controlled trial of doxycycline 100 mg po BID to slow the progression of emphysema as quantified by diffusing capacity for carbon monoxide (DLCO) among PLWH who are current or former smokers. Participants will be stratified by smoking status (current vs former smoker) and clinical site, utilizing dynamic randomization. The primary endpoint of the study is the rate of decline (slope) of percent predicted DLco corrected for hemoglobin, carboxyhemoglobin and barometric pressure over the 72-week treatment period. Our clinical collaborators have successfully demonstrated the feasibility of this study in their NHLBI-funded pilot study to test the safety and tolerability of doxycycline in 27 individuals over 24 weeks (NCT 01744093), and have assembled a group of experienced clinical sites. The DEPTH trial will extend their promising pilot data to a formal phase II clinical trial. An experienced data coordinating center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan (UM) Statistical Analysis of Biomedical and Educational Research (SABER) unit in a top-ranked department of biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, project management, study monitoring, database design and data management, software development, and research administration. SABER has a strong track record of collaborations with Weill Cornell Medicine pulmonary team as the clinical coordinating center (CCC). The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims: (1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze, and disseminate research findings; (2) Ensure the collection of timely, accurate and reproducible data, and maximize adherence to the study protocol; and (3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders. Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on the benefits of doxycycline in PLWH who have emphysema. We anticipate that upon completion of this proposed study, our data will support repurposing the inexpensive antibiotic doxycycline, to slow emphysema progression in PLWH, and demonstrate that it is safe and well tolerated.

DEPTH 试验代表了一种减缓肺气肿进展的创新方法 艾滋病毒感染者（PLWH），这是一个加速疾病进展的人群，目前尚无有效的治疗方法 靶向治疗。我们与 CCC 合作者一起提出了一项 II 期、多中心、随机、双盲、 强力霉素 100 mg 每日两次口服以减缓肺气肿进展的安慰剂对照试验，定量如下： 当前或曾经吸烟的 PLWH 中一氧化碳 (DLCO) 的扩散能力。参加者 将利用动态随机化，根据吸烟状况（当前吸烟者与以前吸烟者）和临床部位进行分层。 该研究的主要终点是预测 DLco 校正百分比的下降率（斜率） 72 周治疗期间的血红蛋白、碳氧血红蛋白和气压。我们的临床 合作者在 NHLBI 资助的试点研究中成功证明了这项研究的可行性 在 24 周内对 27 名个体测试强力霉素的安全性和耐受性 (NCT 01744093)，并已 集合了一批经验丰富的临床现场。 DEPTH 试验将把他们有希望的试点数据扩展到 正式II期临床试验。 经验丰富、具有强大统计领导力和专业知识的数据协调中心 (DCC) 是关键 设计和分析，特别是在临床试验过程中出现意外问题时。这 密歇根大学 (UM) 生物医学和教育研究 (SABER) 单位的统计分析 一流的生物统计学系将作为 DCC，汇集了经验丰富的教师团队和 生物统计学、项目管理、研究监测、数据库设计和数据管理、软件方面的工作人员 开发和研究管理。 SABRE 与 Weill 有着良好的合作记录 康奈尔医学肺科团队作为临床协调中心（CCC）。 UM 的总体目标 DCC 将与研究研究者、CCC 和 NHLBI 合作，以成功实现 按时并在预算范围内学习。我们将通过三个具体目标来实现这些目标：（1）增强 通过提供统计和临床试验方法专业知识来设计、分析和确定科学严谨性 传播研究成果； (2) 确保收集及时、准确和可重复的数据，以及 最大限度地遵守研究方案； (3) 提供已建立的学习基础设施和服务 管理和运营以及研究利益相关者之间的沟通。我们的领导力、经验、 和专业知识将促进合作、鼓励科学生产力并促进及时传播 关于多西环素对肺气肿感染者的益处的研究结果。我们预计完成后 在这项拟议的研究中，我们的数据将支持重新利用廉价的抗生素多西环素，以减缓 PLWH 中肺气肿的进展，并证明其安全且耐受性良好。