Comparative Effectiveness of Biofeedback, Sacral Nerve Stimulation, and Injectable Bulking Agents for Treatment of Fecal Incontinence

 描述（由申请人提供）：3%的美国成年人至少每周发生一次大便失禁，对生活质量有重大影响。生物反馈，骶神经电刺激（SNS），和肛门注射右旋糖酐，惰性填充剂，一直提倡，但缺乏研究直接比较它们，缺乏了解其病理生理基础的进展是关键的障碍。我们的中心假设是，生物反馈比右旋糖酐注射液或SNS更有效、更安全、成本更低。我们提出了一个两步的过程来解决这一重大的知识差距：第一步是U34计划拨款，以最终确定治疗方案，并确认获得足够数量的合格患者，而第二步是U 01多中心随机对照试验（RCT），旨在使用统一的纳入标准，设计和终点来比较这三种治疗方法。U34规划第1年和第2年的具体目标：（1）完成程序手册。(2)为研究管理网站、电子症状日志、数据质量检查和统计分析制定详细计划。(3)制定安全监测计划; NIDDK将任命数据安全监测委员会。(4)通过在所有研究中心进行调查，评估招募策略的可行性。(5)就设备、供应品、技术支持与工业界谈判协议。(6)开发IRB应用程序并开始ClinicalTrials.gov注册。(7)招募、培训和认证生物反馈 干涉主义者(8)最终确定项目治理计划。U 01的具体目标：（1）在387例最佳保守治疗失败的中重度FI男性和女性患者中比较这三种治疗的有效性、安全性和成本。疗效的主要测量将是与基线相比FI发作减少>75%。安全性将通过不良事件的数量来衡量，成本将从个人和社会的角度来衡量。次要终点包括经验证的FI严重程度和生活质量量表。将在6、12和24个月时评估结局。(2)确定可预测对每种干预的反应的基线患者特征。(3)通过比较治疗前后肛门括约肌压力、直肠感觉阈值、直肠顺应性、神经生理学参数和粪便硬度，确定每种干预治疗成功的机制基础。(4)评价治疗组合。6个月内无应答者将被邀请接受另外两种干预措施之一作为额外治疗。(5)评估保守治疗反应的预测因子和获益的持久性。本研究将由北卡罗来纳州大学、马约诊所、明尼阿波利斯的结肠和直肠外科协会、格鲁吉亚摄政大学和北卡罗来纳州RTI国际的数据协调中心（DCC）进行。预期结果包括确定中重度大便失禁的最佳治疗方法，该方法基于机械原理，持久且安全。我们项目的影响将包括对三种常用治疗方式的比较有效性和安全性的新理解，每种治疗的科学依据，以及预测临床结果的因素的识别。

 DESCRIPTION (provided by applicant): Fecal incontinence occurs at least weekly in 3% of U.S. adults and has a significant impact on quality of life. Biofeedback, sacral nerve electrical stimulation (SNS), and anal injection of dextranomer, an inert bulking agent, have been advocated, but absence of studies directly comparing them, and lack of understanding their pathophysiological basis are critical barriers to progress. Our central hypothesis is that biofeedback is more effective, safer, and less costly than dextranomer injection or SNS. We propose a two-step process to address this significant knowledge gap: Step 1 is a U34 planning grant to finalize treatment protocols and confirm access to sufficient numbers of eligible patients, while Step 2 is a U01 multicenter randomized controlled trial (RCT) designed to compare these three treatments using uniform inclusion criteria, design, and endpoints. Specific aims of U34 Planning Years 1 and 2: (1) Finalize procedure manuals. (2) Develop detailed plans for a study management website, electronic symptom diary, data quality checks, and statistical analysis. (3) Develop the safety monitoring plan; NIDDK will appoint Data Safety Monitoring Board. (4) Assess feasibility of recruitment strategy by surveys at all sites. (5) Negotiate agreements with industry for equipment, supplies, technical support. (6) Develop IRB applications and begin ClinicalTrials.gov registration. (7) Recruit, train, and certify biofeedback interventionists. (8) Finalize plans for project governance. Specific aims of U01: (1) Compare effectiveness, safety, and cost of these three treatments in 387 male and female patients with moderate to severe FI who have failed best-practice conservative treatment. The primary measure of efficacy will be >75% reduction in FI episodes compared to baseline. Safety will be measured by number of adverse events, and cost will be measured from both the personal and societal perspectives. Secondary endpoints include validated FI severity and quality of life scales. Outcomes will be assessed at 6, 12, and 24 months. (2) Identify baseline patient characteristics that predict response to each intervention. (3) Identify the mechanistic basis for treatment success for each intervention by comparing pre to post anal sphincter pressures, rectal sensory thresholds, rectal compliance, neurophysiological parameters, and stool consistency. (4) Evaluate treatment combinations. Non-responders by 6 months will be invited to receive one of the other two interventions as additional therapy. (5) Assess predictors of response to conservative treatment and durability of benefits. The study will be conducted by University of North Carolina, Mayo Clinic, Colon and Rectal Surgery Associates of Minneapolis, Georgia Regents University, and a data coordinating center (DCC) at RTI International in North Carolina. Expected outcomes include identifying the best treatment for moderate to severe fecal incontinence that is mechanistically based, durable, and safe. The impact of our project will include new understanding of the comparative effectiveness and safety of three commonly used treatment modalities, a scientific basis for each treatment, and identification of factors that predict clinical outcome.