Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Alimentiv Inc, London, Ontario, Canada.
Gastroenterology. 2024 Jan;166(1):88-102. doi: 10.1053/j.gastro.2023.08.051. Epub 2023 Sep 11.
BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
背景与目的：需要开发安全有效的药物治疗选择来治疗乳糜泻（CeD）；然而，在该人群中，对于随机对照试验（RCT）的适当设计和配置尚未达成共识。
方法：进行了两轮改良的研究与开发/加州大学洛杉矶分校适宜性方法研究。18 名胃肠病学家（成人和儿科）和胃肠病学家对与 CeD RCT 配置、纳入和排除标准、谷蛋白挑战以及试验结果相关的陈述进行了投票。考虑了两种 RCT 设计，代表了可能用于药物治疗的以下两种截然不同的临床情况：纳入谷蛋白挑战以模拟暴露的试验；以及评估组织学变化逆转的试验，尽管尝试坚持无麸质饮食。每个陈述均使用 9 分李克特量表评定为适当、不确定或不适当。
结果：对于评估谷蛋白挑战后复发预防的试验，应招募坚持无麸质饮食 12 个月或更长时间且绒毛正常或接近正常大小的参与者。谷蛋白挑战应不含 FODMAPS（可发酵寡糖、双糖、单糖和多元醇），并使用组织学和次要患者报告结局测量进行疗效评估。对于评估绒毛萎缩逆转的试验，小组投票认为适当招募基线绒毛高度与隐窝深度比≤2 的参与者，并使用主要组织学终点评估疗效。为 CeD 成人和儿科患者提供了组织学、内镜和患者报告结局测量的指南，并就不同终点的优点和局限性提出了建议。
结论：我们为 CeD 患者的 RCT 设计、纳入标准、结局测量、谷蛋白挑战和疾病评估制定了标准化建议。
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