Pilot Study of Zinc Acetate for Chronic Cough

 描述（由申请人提供）：咳嗽是初级保健医生最常见的疾病。慢性咳嗽的定义是持续时间超过8周。慢性顽固性咳嗽，尽管治疗特定的加重条件或经验性治疗没有反应，占高达20%的新的肺部专科转诊。一般的科学共识是，这些患者患有气道咳嗽受体的超敏反应。然而，少数可用的止咳治疗选择受到不良反应、缺乏疗效和滥用可能性的限制。最近的证据已经确定了人类气道的关键咳嗽受体，并确定了调节这些受体敏感性的Na-K-ATP酶的特异性同种型。二价阳离子锌是这种酶的相对特异性阻断剂，并降低动物模型中的咳嗽敏感性。在人类中，足够剂量的锌可有效减少鼻病毒感染后的咳嗽持续时间。此外，锌作为营养补充剂和威尔逊病的治疗具有很强的安全记录。因此，我们提出了两项研究，以告知醋酸锌150 mg/天（Galzin（r））治疗慢性难治性咳嗽患者的确定性试验的设计和可行性。第一项研究是一项先导性随机临床试验，在36名患者中每日接受placbo或150 mg醋酸锌治疗。这项试验将决定一项最终试验是否可行和非徒劳。第二项研究是对100例患者的小组研究，以确定拟议的患者报告的咳嗽结局指标的统计学和心理测量学特征。这些试验将由美国肺脏协会航空临床研究中心（ALA-ACRC）进行，该中心在临床试验方面有着长期的成功记录。

 DESCRIPTION (provided by applicant): Cough is the most common medical condition presenting to primary care physicians. Chronic cough is defined by persistence longer than eight weeks. Chronic refractory cough that does not respond despite treatment for specific aggravating conditions or empiric treatment accounts for up to 20% of new pulmonary specialist referrals. The general scientific consensus is that such patients suffer from hypersensitivity of the airway cough receptors. However, the few available antitussive treatment options are limited by adverse effects, lack of efficacy, and abuse potential. Recent evidence has identified the key cough receptors of the human airway and has identified the specific isoform of Na-K-ATPase that modulates the sensitivity of these receptors. The divalent cation Zinc is a relatively specifi blocker of this enzyme and decreases cough sensitivity in animal models. In humans, Zinc in adequate doses has been effective in reducing cough duration after rhinovirus infections. Further, zinc has a strong safety record as a nutritional supplement and as a treatment for Wilson's disease. Accordingly, we are proposing two studies to inform the design and feasibility of a definitive trial of zinc acetate 150 mg/day (Galzin (r)) for patients with chronic refractory cough. The first study is a pilot randomized clinical trial in 36 patients treated with either placbo or 150 mg Zinc acetate daily. This trial will determine whether a definitive trial is feasible and non-futile. The second study is a panel study of 100 patients to determine the statistical and psychometric characteristics of the proposed patient-reported cough outcome measures. The trials will be conducted by the American Lung Association Airways Clinical Research Centers (ALA-ACRC) which has a long-standing successful track record for clinical trials.