随机、安慰剂对照试验：实验性钩虫感染改善乳糜泻的麸质耐受性。
Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.
机构信息
The Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, Australia.
Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
出版信息
Clin Transl Gastroenterol. 2020 Dec;11(12):e00274. doi: 10.14309/ctg.0000000000000274.
INTRODUCTION
Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled.
METHODS
We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year).
RESULTS
Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6]).
DISCUSSION
Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.
引言
乳糜泻是一种自身免疫性疾病，在摄入麸质后会引起肠道免疫病理学变化。先前的研究表明，钩虫感染可恢复对麸质的耐受性；然而，这些研究规模较小（n=12），且未设安慰剂对照。
方法
我们对 54 名乳糜泻患者进行了钩虫感染的随机、安慰剂对照试验。这项为期 94 周的研究包括用 20 或 40 条美洲钩虫第三期幼虫（L3-20 或 L3-40）或安慰剂进行治疗，随后逐渐增加麸质摄入量（12 周内每天 50mg，12 周内每周两次间歇性摄入 1g，6 周内每天 2g，持续 1 年自由饮食）。
结果
在第 42 周（主要结局），各组的成功完成研究率相似（安慰剂组：57%，L3-20 组：37%，L3-40 组：44%；P=0.61），然而，钩虫治疗组的与麸质相关的不良事件显著减少：中位数（范围）不良事件/参与者如下：安慰剂组，4（1-9）；L3-20 组，1（0-9）；L3-40 组，0（0-3）（P=0.019）。与各自的招募值相比，十二指肠绒毛高度：隐窝深度在各组中均相似恶化（平均变化[95%置信区间]：安慰剂组，-0.6[-1.3 至 0.2]；L3-20 组，-0.5[-0.8 至 0.2]；L3-40 组，-1.1[-1.8 至 0.4]；P=0.12）。回顾性分析显示，40 名接受 L3 治疗的参与者中有 9 名未能建立钩虫感染。尽管钩虫阳性与钩虫阴性参与者的第 42 周完成率相似（48%比 44%，P=0.43），但在间歇性摄入较低、间歇性麸质剂量后，钩虫阳性参与者的生活质量症状评分较低（平均值[95%置信区间]：38.9[33.9-44]比 45.9[39.2-52.6]）。
讨论
钩虫感染不能恢复对持续适量摄入（2g/d）的麸质的耐受性，但与间歇性摄入较低、间歇性麸质剂量后症状评分的改善有关。
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