Balloon Dilation in Selected Subjects with Refractory Eustachian Tube Dysfunction

描述（由申请人提供）：咽鼓管（ET）是中耳（ME）和鼻咽（NP）之间的潜在通信通道。ET的管腔通常是封闭的，但可以通过舌旁肌的活动暂时打开。众所周知，渗出性中耳炎（OME）患者的ET开启功能（ETF）受损，而本构性ET功能障碍（ETD）可导致该疾病作为慢性疾病持续存在。没有标准的药物治疗能有效改善ETF或长期解决持续性OME，通常的治疗方法是插入通气管（vt），绕过ET以保持ME与环境之间的开放沟通。然而，成人室速的功能半衰期约为4-9个月，当室速挤压或无功能时，疾病常复发。最近，一种替代的，也许是更永久的手术治疗ETD，气囊扩张（BDET），已经被描述为相对容易操作，安全有效地解决OME，并且正在积极推广给实践外科医生。然而，少数评估该方法疗效的临床研究样本量小，对“治愈”的定义不明确，而且没有随机、盲法或假对照。重要的是，没有一项研究评估了该程序对ETF的直接影响。在此，我们建议进行一项试点研究，以确定在改善BDET ETF方面的安全性和有效性。在2年的时间里，我们将确定年龄在18-50岁之间的健康患者，这些患者将静脉导管置入作为治疗由ETD引起的OME的方法。40名为实验性单侧BDET提供知情同意的患者将被纳入研究。他们将进行基线ETF测试和内窥镜ET/NP评估，以记录是否存在ETD。将对ETD患者进行3种可降低ETF评分的常见情况的评估：过敏、鼻窦炎和胃食管反流病。如果诊断出某种疾病，受试者将接受适当的医学治疗；否则，他们将接受鼻内类固醇治疗。将重复ETF测试和鼻内窥镜检查，20名对药物治疗无反应的ETD受试者将在麻醉监护下进行单侧BDET。为了安全和测量ET的腔内几何形状，在手术前将完成一份针对ET和ME的修改后的CT方案。将在BDET后1、3和6个月重复ETF测试和内窥镜评估，并在3个月重复CT扫描。对数据进行分析，以确定未选择的成人OME患者发生ETD的频率和原因；确定合并症或炎症的短期医学治疗是否可用于取消受试者考虑BDET的资格，确定与手术相关的并发症的类型和频率，描述手术对ETF和ET管腔几何形状的影响。这些结果将决定是否有必要进行多中心II/III期临床试验。

DESCRIPTION (provided by applicant): The Eustachian tube (ET) is a potential communication between the middle ear (ME) and nasopharynx (NP). The lumen of the ET is usually closed but can be transiently opened by the activity of the paratubal muscles. It is known that the ET opening function (ETF) is impaired in patients presenting with otitis media with effusion (OME) and that constitutive ET dysfunction (ETD) can cause the persistence of the disease as a chronic condition. No standard medical therapy is effective in improving ETF or in resolving persistent OME long-term and the usual treatment is insertion of ventilation tubes (VTs) which bypasses the ET to maintain an open communication between the ME and environment. However, the functional half-life of a VT in adults is approximately 4-9 months and the disease often recurs when the VT is extruded or becomes non-functional. Recently, an alternative and perhaps more permanent surgical treatment for ETD, balloon dilation of the ET (BDET), has been described as being relatively easy to perform, safe and efficacious in resolving OME and is being actively promoted to practicing surgeons for adoption in their practices. However, the few clinical studies that evaluated the efficacy of the procedure included small sample sizes, a weak definition of "cure" and were not randomized, blinded or sham controlled. Importantly, none of the studies evaluated the direct effect of the procedure on ETF. Here, we propose to conduct a pilot study to define the safety and efficacy with respect to improving ETF of BDET. Over a 2-year period, we will identify otherwise healthy patients between 18-50 years of age who have VTs inserted as a treatment for OME caused by ETD. Forty of the patients who provide informed consent for experimental, unilateral BDET will be enrolled as subjects in the study. They will have baseline ETF tests and endoscopic ET/NP evaluations to document the presence or absence of ETD. The subset of subjects with ETD will be evaluated for 3 common conditions that can down-grade ETF: allergy, sinusitis and gastro-esophageal reflux disease. If a condition is diagnosed, the subject will be treated medically as appropriate; otherwise, they will be treated with intranasal steroids. ETF tests and nasal endoscopic examinations will be repeated and 20 subjects with ETD unresponsive to medical treatment will have unilateral BDET done under monitored anesthesia care. For safety and measurement of ET luminal geometry, a modified CT protocol focused on the ET and ME will be done prior to the procedure. ETF tests and endoscopic evaluations will be repeated at 1, 3 and 6 months and the CT scan will be repeated at 3 months after the BDET. The data will be analyzed to: define the frequency and cause of ETD in unselected adults with OME; determine if a short course of medical treatment for co-morbid conditions or for inflammation can be used to disqualify subjects from consideration for BDET, identify the type and frequency of complications associated with the procedure, describe the effect of the procedure on ETF and ET luminal geometry. These results will determine if a multi-center, phase II/III clinical trial ofthe procedure is warranted.