Combining Necator Americanus With Trace Gluten to Restore Tolerance in Coeliac Disease: a Pilot Clinical and a Detailed in Vitro Immunological Study.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Duodenal Villus Height:Crypt Depth
研究概览
简要总结
We have established that the hookworm Necator americanus (Na) dramatically alters the local and systemic immune landscape of the infected human host. Consistent with the principle of desensitisation, diet managed celiac disease subjects previously infected by us with Na will be invited to receive small incremental doses of gluten as pasta (3-25 mm straw of spaghetti) over 16 weeks. Each participant will then be carefully re-assessed to determine if it is appropriate to undertake a 12-week gluten challenge.
详细描述
Hypothesis The adaptive Th2/regulatory profile imposed by Na will promote gluten tolerance following a micro-dose desensitising programme.
Primary Aim: To determine the safety and efficacy of Na as a tolerising agent in celiac subjects
Specific Aim 1. Undertake a therapeutic pilot study comparing mucosal histopathology before and after a gluten challenge, to be preceded by a programmed desensitising micro-challenge using Na as a tolerising agent.
Specific Aim 2. Assess systemic and mucosal immune responses to gluten micro-challenge, Na infection, and gluten re-challenge throughout the pilot study, to be referenced against hookworm-naive people with treated and untreated celiac disease.
Specific Aim 3. Utilising blood and tissue from hookworm-naive celiac disease volunteers, undertake in vitro studies focusing on the effects of Na-derived excretory/secretory (ES) products on gluten-stimulated gut mucosal cell apoptosis, cytokine and gene profiles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previously enrolled adults who received an experimental hookworm infection with diet treated celiac disease.
排除标准
- •Immune suppressive therapies
研究组 & 干预措施
Necator americanus, gluten challenge
Single arm, vertical.
干预措施: Necator americanus (Biological)
结局指标
主要结局
Duodenal Villus Height:Crypt Depth
时间窗: Week -24 to -36
Biopsies were fixed in neutral buffered formalin, processed and carefully orientated and embedded in paraffin wax. Sections (3 µm) were stained with H\&E. Slides from both time-points were de-identified, shuffled and graded by Dr John Croese after which results from poorly orientated slides were verified by Dr Andrew Clouston. The Vh:Cd ratios were measured on 5 randomly selected well-orientated sites. The null hypothesis is that hookworm infection will not protect against mucosal damage following 12-week exposure to gluten in celiac disease.
次要结局
- Intraepithelial Lymphocyte Count(Week-24 and -36)
- Number of Participants With 2 Points Increase in Marsh Score Post GC-1g(Longitudinal change between week-24 and week-36)
- Serum Anti-tissue Transglutaminase Antibodies Measured as International Units/mL (IU/mL)(Anti-tTG IU/mL levels pre-trial, mid-trial and after 3 gram/day gluten challenge)
研究者
Dr John Croese
Chief Investigator
The Prince Charles Hospital