Stefanolo Juan Pablo, Segura Verónica, Grizzuti Martina, Heredia Abel, Comino Isabel, Costa Ana Florencia, Puebla Roberto, Temprano María Paz, Niveloni Sonia Isabel, de Diego Gabriel, Oregui María E, Smecuol Edgardo Gustavo, de Marzi Mauricio C, Verdú Elena F, Sousa Carolina, Bai Julio César
Small Bowel Section, Department of Medicine, Gastroenterology Hospital of Buenos Aires "Dr. C. Bonorino Udaondo", Buenos Aires 1264, Argentina.
Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville 41080, Spain.
World J Gastroenterol. 2024 Mar 21;30(11):1545-1555. doi: 10.3748/wjg.v30.i11.1545.
BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 μg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 μg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 μg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower ( < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.
背景：无麸质饮食（GFD）存在局限性，目前针对辅助治疗的研发正在深入开展。 目的：研究口服脯氨酰内肽酶蛋白酶（AN - PEP）对成年乳糜泻（CeD）患者在遵循常规GFD饮食时意外摄入麸质及症状预防的影响。 方法：这是一项探索性、双盲、随机、安慰剂对照试验，纳入长期遵循GFD饮食的CeD患者。经过4周的导入期后，患者被随机分为两组，一组在每日三餐时各服用两粒AN - PEP胶囊（GliadinX；AVI Research，LLC，美国），共服用4周，另一组服用安慰剂。观察终点包括：（1）导入期与治疗结束时以及AN - PEP组与安慰剂组之间每周粪便中麸质免疫原性肽（GIP）的平均含量；（2）乳糜泻症状指数（CSI）；（3）CeD特异性血清学指标；（4）生活质量。在导入期和治疗期间，每周二和周五采集粪便样本，通过酶联免疫吸附测定（ELISA）检测GIP。 结果：40例患者被随机纳入意向性分析，3例被排除在符合方案分析之外。总体而言，共采集了628/640（98.1%）份粪便样本。65.6%的样本中未检测到GIP（<0.08μg/g），且各治疗组之间未检测到差异。只有0.5%的样本GIP浓度足够高（>0.32μg/g），可能会导致黏膜损伤。AN - PEP组的GIP中位数浓度比导入期低44.7%。在导入期GIP>0.08μg/g的患者中，三分之一在接受AN - PEP治疗后GIP降低或检测不到。与导入期相比，AN - PEP组有症状患者（CSI>38）的比例显著降低（<0.03）。AN - PEP未导致特异性血清学指标发生变化。 结论：在实际生活环境中进行的这项探索性研究表明患者对GFD的依从性较高。AN - PEP治疗并未显著降低粪便中GIP的总体浓度。然而，鉴于观察到AN - PEP组严重症状患者的患病率显著较低，有必要进一步开展临床研究。
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