Pilot Study of Zinc Acetate for Chronic Cough

醋酸锌治疗慢性咳嗽的初步研究

• 批准号: 9115284
• 负责人: BRENDAN J CANNING
• 金额: $ 28.53万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115284
• 关键词: Accounting; Acute; Address; Adverse effects; American Lung Association; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Antitussive Agents; Asthma; Characteristics; Chemicals; Chronic; Clinical Research; Clinical Trials; Consensus; Consultations; Coughing; Disease; Distress; Divalent Cations; Dose; Enrollment; Enzymes; Fatigue; Futility; Gastroesophageal reflux disease; Guidelines; Health; Hepatolenticular Degeneration; Human; Hypersensitivity; Impairment; Infection; Isoenzymes; Laboratories; Lung; Lung diseases; Measures; Mechanics; Medical; Mucositis; Multicenter Trials; Na(+)-K(+)-Exchanging ATPase; Nose; Oral; Outcome Measure; Participant; Patients; Pilot Projects; Primary Care Physician; Property; Protein Isoforms; Psychometrics; Quality of life; Randomized; Randomized Clinical Trials; Refractory; Reporting; Rhinovirus; Safety; Sinusitis; Site; Sleep Deprivation; Smoking; Social isolation; Specialist; Upper Respiratory Infections; Zinc; Zinc Acetate; Zinc supplementation; afferent nerve; airway hyperresponsiveness; base; cohort; design; dietary supplements; effective therapy; irritation; medical specialties; novel therapeutics; pre-clinical; public health relevance; receptor; receptor sensitivity; tool

 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.

 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八周。尽管针对特定加重病症进行治疗或经验性治疗仍没有缓​​解的慢性难治性咳嗽占新转诊肺科专家的 20%。普遍的科学共识是，此类患者患有气道咳嗽受体过敏。然而，少数可用的镇咳治疗方案受到不良反应、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 酶的特定亚型。二价阳离子锌是这种酶的相对特异性阻断剂，可降低动物模型中的咳嗽敏感性。对于人类来说，足够剂量的锌可以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氏病的治疗方法具有良好的安全记录。因此，我们提出两项研究，为慢性顽固性咳嗽患者使用醋酸锌 150 毫克/天 (Galzin (r)) 的最终试验的设计和可行性提供信息。第一项研究是一项试点随机临床试验，共有 36 名患者接受安慰剂或每日 150 毫克醋酸锌治疗。该试验将确定最终试验是否可行且不会徒劳。第二项研究是一项针对 100 名患者的小组研究，旨在确定拟议的患者报告的咳嗽结果指标的统计和心理测量特征。这些试验将由美国肺脏协会航空公司临床研究中心 (ALA-ACRC) 进行，该中心在临床试验方面拥有长期成功的记录。