Study on The Effectiveness of Oral Administration of Prolyl Endoprotease for Gluten Detoxification as a Means to Treat Coeliac Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Histopathological changes according to the Modified Marsh criteria
研究概览
简要总结
Oral supplementation with enzymes that can cut gluten has been suggested as a potential treatment modality for coeliac disease. In the present study the investigators wish to determine if co-administration of such an enzyme, a prolyl endoprotease derived from the food grade organism Aspergillis niger (AN-PEP), is capable of detoxifying 8 grams of gluten in a commercial food product.
详细描述
The objective of the study is to determine whether AN-PEP enzyme is effective in mitigating the effects of 8 g wheat protein ingestion in patients with celiac disease.
Fourteen patients with coeliac disease, 18-70 years old are recruited. During the first period, patients consume once daily a gluten-containing food product with the AN-PEP enzyme for 2 weeks. After a 2-week washout period (second period), patients enter the third period of this study, and are randomized to one of two groups and consume the same gluten-containing food product with AN-PEP or placebo.
Period 1: Patients are given a food product containing 8 g of wheat protein, to which AN-PEP is added, once daily for 14 d.
Period 2: Wash-out period of 14 d. During this period, patients will consume a gluten-free diet.
Period 3: Patients who are negative for coeliac disease symptoms during the 1st period will be randomized across two groups. Both groups receive a food product containing 8 g of wheat protein once daily for 14 d. One group receives additional AN-PEP with the gluten meal whereas the other group receives the placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of coeliac disease (Marsh III B/C) ; that means crypt hyperplasia and subtotal or total villous atrophy, while using a normal diet followed by normalisation and clinical improvement on a gluten-free diet;
- •Detectable coeliac disease specific antibodies (EMA, tTGA) at time of diagnosis.
- •A strict gluten free diet for at least 1 year and normalised villous architecture (Marsh 0/I);
- •Male and female, 18-70 years old;
- •No detectable anti-endomysium and low anti-tissue transglutaminase (< 4 U/ml) prior to the start of the study;
- •Patient is willing to undergo all protocol related assessments and visits (including up to 3 separate oesophago-gastro-duodenoscopies with multiple biopsies taken each time from the descending duodenum);
- •Patient has read the information provided on the study and given written consent;
- •Female participants at fertile age must use adequate contraception.
排除标准
- •Use of any immunoregulatory drug within the last 6 months;
- •Use of any anticoagulant drug;
- •Clinically suspected bleeding tendency;
- •Pregnancy or breast feeding;
- •Presence of any concurrent active infection;
- •IgA deficiency.
结局指标
主要结局
Histopathological changes according to the Modified Marsh criteria
时间窗: One week before start, and 2 and 6 weeks after start
The presence of coeliac disease specific antibodies (EMA, tTGA, gliadin)
时间窗: One week before start, and 2 and 6 weeks after start
次要结局
- Presence and activity of gluten reactive Tcells isolated from biopsies and serum(One week before start, and 2 and 6 weeks after start)
- Immunophenotype of lymphocytes isolated from biopsies(One week before start, and 2 and 6 weeks after start)
- Clinical symptoms after gluten intake with and without AN-PEP(One week before start, and 2 and 6 weeks after start)