Doxycycline for COPD in HIV-Infected Patients

多西环素治疗 HIV 感染者的慢性阻塞性肺病

基本信息

  • 批准号:
    8445031
  • 负责人:
  • 金额:
    $ 57.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-27 至 2014-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is emerging as an important cause of morbidity in HIV-infected patients, likely due to multiple factors, including an increased prevalence of smoking, chronic inflammation and immune activation, oxidant stress and respiratory infections. Our preliminary data suggest that several lung matrix metalloproteinases (MMPs) are upregulated in HIV-infected smokers, which could contribute to accelerated emphysema by virtue of their ability to degrade extracellular matrix and basement membrane components. Based on these observations, we hypothesize that pharmacologic inhibition of MMPs by doxycycline, the only FDA-approved inhibitor of MMPs, will favorably modify the natural history of COPD in HIV-infected patients. To test this hypothesis, we propose conducting a phase II randomized, placebo-controlled trial of doxycycline for COPD in HIV-infected patients. Our research team, led by a pulmonologist / translational researcher with expertise in HIV-associated COPD and an infectious diseases specialist/clinical trials expert, is well positioned to propose such a trial to the NIH-funded AIDS Clinical Trials Group (ACTG). To achieve this end, we first propose to conduct a pilot study to enable us to address the following Specific aims: Aim 1. To determine the safety, tolerability, and biologic effects of twice daily doxycycline for 6 months in HIV-infected subjects with COPD; and Aim 2. To prepare and submit an application for a phase II clinical trial of doxycycline for COPD in HIV-infected subjects. To address the first aim, we will conduct a randomized, double-blind, placebo-controlled pilot study of doxycycline 100 mg twice daily in 30 HIV-infected subjects with COPD (2:1 doxy:placebo). The primary endpoint will be safety/tolerability and secondary endpoints will include change in FEV1, reduction of MMP activity in epithelial lining fluid and cells obtained by bronchoscopy and doxycycline levels in blood, ELF and BAL cell pellets. In addition to providing novel insights into the biologic effects of doxycycline in the lung, the pilot study will inform selection of endpoints for a phase II trial, which ultimately will address an unmet medical need for novel interventions for COPD/emphysema in HIV-infected patients. PUBLIC HEALTH RELEVANCE: Chronic obstructive lung disease (COPD)/emphysema is an important public health problem in the general population and, in particular, in HIV-infected patients. The proposed work is testing a novel intervention for this disorder that, if successful, has the potential to reduce the progression of COPD/emphysema. The findings from the proposed work will have implications for all persons with COPD/emphysema, regardless of HIV status.
描述(由申请方提供):慢性阻塞性肺疾病(COPD)正在成为HIV感染患者发病的重要原因,可能是由于多种因素,包括吸烟、慢性炎症和免疫激活、氧化应激和呼吸道感染的患病率增加。我们的初步数据表明,几种肺基质金属蛋白酶(MMPs)在HIV感染的吸烟者中上调,这可能有助于加速肺气肿凭借其降解细胞外基质和基底膜成分的能力。基于这些观察结果,我们假设强力霉素(FDA唯一批准的MMPs抑制剂)对MMPs的药理学抑制将有利地改变HIV感染患者的COPD自然史。为了验证这一假设,我们建议进行一项II期随机、安慰剂对照的多西环素治疗HIV感染患者COPD的试验。我们的研究团队由一位具有HIV相关COPD专业知识的肺病学家/翻译研究员和一位传染病专家/临床试验专家领导,能够向NIH资助的艾滋病临床试验组(ACTG)提出这样的试验。为了达到这个目的,我们首先建议进行一项试验研究,使我们能够实现以下具体目标:确定多西环素每日两次持续6个月在HIV感染的COPD受试者中的安全性、耐受性和生物学效应;目的2。准备并提交多西环素治疗HIV感染者COPD的II期临床试验申请。为了实现第一个目标,我们将在30名患有COPD的HIV感染受试者中进行一项随机、双盲、安慰剂对照的多西环素100 mg每日两次的初步研究(2:1的多西环素:安慰剂)。主要终点将是安全性/耐受性,次要终点将包括FEV 1的变化、通过支气管镜检查获得的上皮衬里液和细胞中MMP活性的降低以及血液、ELF和BAL细胞团中的多西环素水平。除了对多西环素在肺部的生物学效应提供新的见解外,该初步研究还将为II期试验的终点选择提供信息,最终将解决HIV感染患者对COPD/肺气肿新型干预措施的未满足的医疗需求。 公共卫生相关性:慢性阻塞性肺病(COPD)/肺气肿是普通人群中的重要公共卫生问题,特别是在HIV感染患者中。拟议的工作是测试这种疾病的新干预措施,如果成功,有可能减少COPD/肺气肿的进展。这项研究的结果将对所有COPD/肺气肿患者产生影响,无论其HIV感染状况如何。

项目成果

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MARSHALL J GLESBY其他文献

MARSHALL J GLESBY的其他文献

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{{ truncateString('MARSHALL J GLESBY', 18)}}的其他基金

1/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial
1/2 强力霉素治疗艾滋病毒感染者肺气肿:DEPTH 试验
  • 批准号:
    10509159
  • 财政年份:
    2021
  • 资助金额:
    $ 57.4万
  • 项目类别:
1/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial
1/2 强力霉素治疗艾滋病毒感染者肺气肿:DEPTH 试验
  • 批准号:
    10703241
  • 财政年份:
    2021
  • 资助金额:
    $ 57.4万
  • 项目类别:
1/2 Doxycycline for Emphysema in People Living with HIV: The DEPTH Trial
1/2 强力霉素治疗艾滋病毒感染者肺气肿:DEPTH 试验
  • 批准号:
    10259295
  • 财政年份:
    2021
  • 资助金额:
    $ 57.4万
  • 项目类别:
Clonal Hematopoeisis in HIV and Aging
HIV 和衰老中的克隆造血
  • 批准号:
    10163768
  • 财政年份:
    2020
  • 资助金额:
    $ 57.4万
  • 项目类别:
Clonal Hematopoeisis in HIV and Aging
HIV 和衰老中的克隆造血
  • 批准号:
    10013829
  • 财政年份:
    2020
  • 资助金额:
    $ 57.4万
  • 项目类别:
Doxycycline for COPD in HIV-Infected Patients
多西环素治疗 HIV 感染者的慢性阻塞性肺病
  • 批准号:
    8554373
  • 财政年份:
    2012
  • 资助金额:
    $ 57.4万
  • 项目类别:
Complications of Chronic Viral Infections
慢性病毒感染的并发症
  • 批准号:
    7646485
  • 财政年份:
    2008
  • 资助金额:
    $ 57.4万
  • 项目类别:
Complications of Chronic Viral Infections
慢性病毒感染的并发症
  • 批准号:
    8091301
  • 财政年份:
    2008
  • 资助金额:
    $ 57.4万
  • 项目类别:
Complications of Chronic Viral Infections
慢性病毒感染的并发症
  • 批准号:
    8287087
  • 财政年份:
    2008
  • 资助金额:
    $ 57.4万
  • 项目类别:
Complications of Chronic Viral Infections
慢性病毒感染的并发症
  • 批准号:
    7494841
  • 财政年份:
    2008
  • 资助金额:
    $ 57.4万
  • 项目类别:

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