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

生物反馈、骶神经刺激和注射填充剂治疗大便失禁的效果比较

• 批准号: 9092194
• 负责人: ADIL E. BHARUCHA
• 金额: $ 38.51万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-20 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9092194
• 关键词: Address; Adherence; Admission activity; Adult; Adverse event; Advertisements; Advocate; Agreement; Anal canal; Anus; Authorship; Biofeedback; Characteristics; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Trials Data Monitoring Committees; Colorectal Surgery; Consent Forms; Data; Data Collection; Data Coordinating Center; Data Quality; Development; Diabetes Mellitus; Diarrhea; Digestive System Disorders; Discipline of Nursing; Educational workshop; Electric Stimulation; Electronics; Equipment and Supplies; Fecal Incontinence; Feces; Female; Frequencies; Funding; Goals; Grant; Individual; Industry; Injectable; Injection of therapeutic agent; Institutes; Institutional Review Boards; International; Intervention; Kidney Diseases; Knowledge; Lead; Manuals; Measures; Mediation; Methods; Modality; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; North Carolina; Outcome; Outcome Study; Participant; Patients; Pelvic floor structure; Physiological; Physiology; Procedures; Process; Protocols documentation; Publications; Quality of life; Randomized; Randomized Controlled Trials; Recording of previous events; Recruitment Activity; Reporting; Research Personnel; Research Priority; Resistance; Sacral nerve; Safety; Sensory Thresholds; Severities; Site; Statistical Data Interpretation; Surveys; Symptoms; System; Technology; TimeLine; Training; Treatment Cost; Treatment Protocols; Universities; alternative treatment; base; comparative effectiveness; compare effectiveness; control trial; cost; cost effective; data management; design; diaries; follow-up; implantable device; inclusion criteria; incontinence symptom; male; meetings; neurophysiology; predict clinical outcome; predicting response; premature; pressure; public health relevance; quality assurance; rectal; response; secondary outcome; sphincter ani muscle structure; success; tocol; treatment choice; treatment response; trial comparing; trial design; volunteer; web portal; web site; willingness

 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.

 描述（由申请人提供）：3% 的美国成年人至少每周都会出现大便失禁，这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（一种惰性填充剂）。已经被提倡，但缺乏直接比较它们的研究，并且缺乏对其病理生理学基础的了解是进展的关键障碍，我们的中心假设是生物反馈更重要。比右旋糖酐注射或 SNS 更有效、更安全且成本更低，我们提出了一个两步流程来解决这一重大知识差距：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。图 2 是一项 U01 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：(1) 最终确定程序手册。 (2) 制定研究管理网站、电子症状日记、数据质量检查和统计分析的详细计划； (3) 制定安全监测计划； (4) 评估招募策略的可行性。 (5) 与行业就设备、用品、技术支持协商协议 (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。 (8) 最终确定 U01 的具体目标： (1) 比较这三种治疗方法对 387 名未能接受最佳实践保守治疗的中度至重度 FI 患者的有效性、安全性和成本。疗效的主要衡量标准是与基线相比，FI 事件减少 75% 以上。安全性将通过不良事件的数量来衡量，而成本将从个人和社会的角度来衡量，次要终点包括经过验证的 FI 严重程度和质量。生命尺度。将在 6、12 和 24 个月时评估结果 (2) 确定预测每次干预反应的基线患者特征 (3) 通过比较肛门括约肌前后压力、直肠压力来确定每次干预治疗成功的机制基础。 (4) 评估治疗组合，6 个月前无反应者将被邀请接受其他两种干预措施之一作为额外治疗。 (5) 评估保守治疗反应和获益持久性的预测因素 该研究将由北卡罗来纳大学、梅奥诊所、​​明尼阿波利斯结肠和直肠外科协会、佐治亚摄政大学以及位于美国的数据协调中心 (DCC) 进行。北卡罗来纳州 RTI International 的预期成果包括确定基于机械的、持久且安全的中度至重度大便失禁的最佳治疗方法。我们项目的影响将包括对三种药物的相对有效性和安全性的新认识。常用的治疗方式、每种治疗的科学依据以及预测临床结果的因素的确定。