Efficacy and Safety of Beta-adrenoceptor Inverse Agonist, Nadolol in Mild Asthma

β-肾上腺素受体反向激动剂纳多洛尔治疗轻度哮喘的疗效和安全性

基本信息

  • 批准号:
    8517571
  • 负责人:
  • 金额:
    $ 165.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-08-15 至 2016-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Asthma is a chronic inflammatory disease of the airways characterized by the presence of reversible airway obstruction and airway hyperresponsiveness. Pharmacological management aims at reversing bronchoconstriction and combating chronic inflammation. Beta2-adrenoceptor (¿-AR) agonists are effective bronchodilators and play a major role in every stage of asthma management. However, their chronic regular use may be associated with detrimental effects including an increase in asthma-related deaths. Conversely, recent pilot data suggest that the chronic use of certain beta-blockers, specifically 3-AR inverse agonists such as nadolol, which are currently contraindicated in asthma, may be associated with attenuation of airway hyperresponsiveness in patients with mild asthma. Studies in the mouse model of asthma suggest that such effects may be related to decreased airway inflammation and mucous metaplasia. We propose a three site, prospective, randomized, double-blind, placebo-controlled study to further investigate the efficacy and safety of chronic nadolol in asthma. The study will enroll 60 subjects with mild asthma. 18-60 years of age, will be of 24 weeks duration. The primary outcome measure will be the change in airway hyperresponsiveness to methacholine (PC20 forced expiratory volume in one second, FEV1). Secondary outcomes will be measures of lung function (FEV1) and asthma control. Exploratory outcomes will investigate the effects of nadolol on indices of airway inflammation as measured in exhaled breath, blood, and induced sputum. A substudy (n = 30) will employ bronchoscopy in a subset of subjects to investigate the effects of nadolol on airway inflammation and mucous metaplasia measured in airway epithelial cells obtained by brushes and airway biopsies. P-AR expression, ligand binding and signaling will be measured in airway epithelial cells and peripheral lymphocytes. Other exploratory outcomes will include genetic analyses to determine if these influence individual responses to nadolol. Safety measures collected throughout the study will include adverse events (AEs), withdrawals due to AEs, serious AEs, pulmonary function measurements, vital signs, and physical examinations.
描述(由申请人提供):哮喘是一种气道慢性炎症性疾病,其特征在于存在可逆性气道阻塞和气道高反应性。药理学管理旨在逆转支气管收缩和对抗慢性炎症。β 2-肾上腺素能受体(<$-AR)激动剂是有效的支气管扩张剂,在哮喘治疗的每个阶段都发挥着重要作用。然而,长期经常使用这些药物可能会产生有害影响,包括增加与哮喘有关的死亡。相反,最近的试点数据表明,长期使用某些β受体阻滞剂,特别是3-AR反向激动剂,如纳多洛尔,目前在哮喘中是禁忌的,可能与轻度哮喘患者气道高反应性的减弱有关。对哮喘小鼠模型的研究表明,这种作用可能与气道炎症和粘膜化生减少有关。我们提出了一个三个地点,前瞻性,随机,双盲,安慰剂对照研究,以进一步探讨慢性纳多洛尔在哮喘的疗效和安全性。本研究将入组60例轻度哮喘受试者。18-60岁,将持续24周。主要结果测量将是气道对乙酰甲胆碱的高反应性的变化(PC 20一秒用力呼气量,FEV 1)。次要结局将是肺功能(FEV 1)和哮喘控制的指标。探索性结局将研究纳多洛尔对呼出气、血液和诱导痰中测量的气道炎症指数的影响。一项子研究(n = 30)将在一个受试者亚组中采用支气管镜检查,以研究纳多洛尔对气道炎症和粘膜化生的影响,这些炎症和粘膜化生是通过刷子和气道活检获得的气道上皮细胞测量的。将在气道上皮细胞和外周淋巴细胞中测量P-AR表达、配体结合和信号传导。其他探索性结果将包括遗传分析,以确定这些是否影响个体对纳多洛尔的反应。整个研究期间收集的安全性指标将包括不良事件(AE)、因AE退出、严重AE、肺功能测量、生命体征和体格检查。

项目成果

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会议论文数量(0)
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NICOLA A HANANIA其他文献

DUPILUMAB IMPROVES RESPIRATORY SYMPTOMS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND TYPE 2 INFLAMMATION: POOLED RESULTS FROM BOREAS AND NOTUS
  • DOI:
    10.1016/j.chest.2024.06.2863
  • 发表时间:
    2024-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    SURYA P BHATT;KLAUS F RABE;NICOLA A HANANIA;CLAUS VOGELMEIER;MONA BAFADHEL;STEPHANIE CHRISTENSON;ALBERTO PAPI;DAVE SINGH;ELIZABETH LAWS;PAULA DAKIN;JENNIFER MALONEY;XIN LU;DEBORAH BAUER;ASHISH BANSAL;RAOLAT ABDULAI;LACEY ROBINSON
  • 通讯作者:
    LACEY ROBINSON
ASSOCIATION OF DYSPNEA-RELATED DISABILITY AND ANXIETY IN PATIENTS WITH COPD
  • DOI:
    10.1016/j.chest.2022.08.1894
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    ABEBAW M YOHANNES;RICHARD CASABURI;SHEILA DRYDEN;NICOLA A HANANIA
  • 通讯作者:
    NICOLA A HANANIA
LUNG MASSES IN ASTHMA: NOT ALWAYS LUNG CANCER!
  • DOI:
    10.1016/j.chest.2023.07.2656
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    SHRUTI REVANKAR;DHARANI KUMARI NARENDRA;NICOLA A HANANIA
  • 通讯作者:
    NICOLA A HANANIA
THE INFLUENCE OF AGE ON THE PREVALENCE AND IMPACT OF ANXIETY IN PATIENTS WITH COPD
  • DOI:
    10.1016/j.chest.2024.06.3388
  • 发表时间:
    2024-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    ABEBAW M YOHANNES;RICHARD CASABURI;NICOLA A HANANIA
  • 通讯作者:
    NICOLA A HANANIA
EFFICACY AND SAFETY OF DUPILUMAB FOR COPD WITH TYPE 2 INFLAMMATION
  • DOI:
    10.1016/j.chest.2023.07.4211
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    SURYA P BHATT;KLAUS F RABE;NICOLA A HANANIA;CLAUS F VOGELMEIER;JEREMY COLE;MONA BAFADHEL;STEPHANIE CHRISTENSON;ALBERTO PAPI;DAVE SINGH;ELIZABETH LAWS;LEDA LM MANNENT;ERIC R MORTENSEN;JENNIFER MALONEY;XIN LU;DEBORAH J BAUER;ASHISH BANSAL;LACEY ROBINSON;RAOLAT ABDULAI
  • 通讯作者:
    RAOLAT ABDULAI

NICOLA A HANANIA的其他文献

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{{ truncateString('NICOLA A HANANIA', 18)}}的其他基金

Efficacy and Safety of Beta-adrenoceptor Inverse Agonist, Nadolol in Mild Asthma
β-肾上腺素受体反向激动剂纳多洛尔治疗轻度哮喘的疗效和安全性
  • 批准号:
    8320144
  • 财政年份:
    2011
  • 资助金额:
    $ 165.64万
  • 项目类别:
Efficacy and Safety of Beta-adrenoceptor Inverse Agonist, Nadolol in Mild Asthma
β-肾上腺素受体反向激动剂纳多洛尔治疗轻度哮喘的疗效和安全性
  • 批准号:
    8143915
  • 财政年份:
    2011
  • 资助金额:
    $ 165.64万
  • 项目类别:
Efficacy and Safety of Beta-adrenoceptor Inverse Agonist, Nadolol in Mild Asthma
β-肾上腺素受体反向激动剂纳多洛尔治疗轻度哮喘的疗效和安全性
  • 批准号:
    8858923
  • 财政年份:
    2011
  • 资助金额:
    $ 165.64万
  • 项目类别:
Response to Beta2-Agonists in Acute Severe Asthma
急性重度哮喘中 Beta2 激动剂的反应
  • 批准号:
    6960206
  • 财政年份:
    2005
  • 资助金额:
    $ 165.64万
  • 项目类别:
Response to Beta2-Agonists in Acute Severe Asthma
急性重度哮喘中 Beta2 激动剂的反应
  • 批准号:
    7479837
  • 财政年份:
    2005
  • 资助金额:
    $ 165.64万
  • 项目类别:
Response to Beta2-Agonists in Acute Severe Asthma
急性重度哮喘中 Beta2 激动剂的反应
  • 批准号:
    7261973
  • 财政年份:
    2005
  • 资助金额:
    $ 165.64万
  • 项目类别:
Response to Beta2-Agonists in Acute Severe Asthma
急性重度哮喘中 Beta2 激动剂的反应
  • 批准号:
    7121044
  • 财政年份:
    2005
  • 资助金额:
    $ 165.64万
  • 项目类别:

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