The Innate Response to and Changes in Intestinal Permeability 4 Hours After a Gluten Challenge in Subjects With Celiac Disease and Non Celiac Gluten Sensitivity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Activation of the Mucosal Innate Immune System after Oral Gluten Challenge
研究概览
简要总结
This study evaluates why people with celiac disease and non-celiac gluten/wheat sensitivity develop rapid onset symptoms within hours of gluten exposure. Half of subjects will be given gluten and half will not.
详细描述
When a person with celiac disease is exposed to gluten, their immune system attacks their bowel and causes abdominal pain, bloating, and diarrhea. This process takes 24-72 hours to occur. Some people without celiac disease develop similar symptoms when they eat gluten or wheat. Doctors and scientists do not know what causes this sensitivity to gluten. People with celiac disease and non-celiac gluten sensitivity report symptoms within hours of being exposed to gluten. This study evaluates why this occurs by looking at changes in blood, urine, stool, and the bowel after being given gluten.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Subjects will be block randomized to either gluten-containing or placebo challenge.
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
- 是
入选标准
- •for subjects with Celiac Disease:
- •Biopsy proven celiac disease diagnosed at least 2 years prior to recruitment
- •Attest to following a gluten free diet to the best of their ability
- •Quiescent symptoms on a gluten free diet
- •Negative tissue transglutaminase at time of recruitment (to be collected with baseline blood work)
- •A prior endoscopy with small bowel biopsies reviewed by a gastrointestinal pathologist revealing healing
- •Inclusion Criteria for subjects with Non-Celiac Gluten Sensitivity:
- •Meet diagnostic consensus criteria as defined by Ludvigsson et al in "The Oslo definitions for coeliac disease and related terms"
- •Attest to following a gluten free diet to the best of their ability
- •Quiescent symptoms on a gluten free diet
- •Prior negative evaluation for celiac disease (including tissue transglutaminase IgA with total IgA or small bowel biopsies)
- •If subjects have had a small bowel biopsies revealing increased intraepithelial lymphocytes (IELs), they will be reviewed as a separate subgroup
- •Inclusion Criteria for Normal Subjects:
- •No gastrointestinal diagnosis (reflux, eosinophilic esophagitis, inflammatory bowel disease, or irritable bowel syndrome)
- •No gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting, weight loss)
- •No family history of celiac disease
- •Will not be required to have a baseline biopsy
排除标准
- •Tobacco use
- •Symptomatic coronary disease
- •Active, severe pulmonary disease
- •Baseline oxygen requirement
- •Coagulopathy (INR>1.5)
- •Mastocytosis
- •Active H. pylori infection
- •Treated celiac disease with neutrophilia or eosinophilia secondary to infection
- •Diabetes (type 1 and type 2)
- •Crohn's disease or Ulcerative colitis
- •Microscopic colitis
- •Dermatitis herpetiformis
- •Gastroparesis
- •Pregnant women
- •Subjects exposed to the following medications during their respective time frames will be excluded:
- •NSAIDs (24 hours)
- •Leukotriene inhibitors (24 hours)
- •Mast cell stabilizers (24 hours)
- •Benzodiazepines (24 hours)
- •H2 blockers (2 days)
- •H1 blockers (7 days)
- •Steroids (systemic or topically active within gastrointestinal tract) (30 days)
- •Topical steroids (14 days)
- •Intermittent (up to once weekly) tranquilizer (trazodone, doxepin) use (7 days)
- •Chronic tricyclic antidepressant or tranquilizer use (trazodone, doxepin) Use of these medications will also be prohibited during the study duration (AAAAI and AAOA).
研究组 & 干预措施
Normal Subjects, Gluten Drink
Normal subjects will drink a solution containing 6 grams of gluten one time.
干预措施: Gluten (Dietary Supplement)
Normal Subjects, Placebo Drink
Normal subjects will drink a solution without gluten one time.
干预措施: Placebo (Dietary Supplement)
Celiac Subjects, Gluten Drink
Subjects with celiac disease will drink a solution containing 6 grams of gluten one time.
干预措施: Gluten (Dietary Supplement)
Celiac Subjects, Placebo Drink
Subjects with celiac disease will drink a solution without gluten one time.
干预措施: Placebo (Dietary Supplement)
Gluten Sensitivity, Gluten Drink
Subjects with non-celiac gluten sensitivity will drink a solution containing 6 grams of gluten one time.
干预措施: Gluten (Dietary Supplement)
Gluten Sensitivity, Placebo Drink
Subjects with non-celiac gluten sensitivity will drink a solution without gluten one time.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Activation of the Mucosal Innate Immune System after Oral Gluten Challenge
时间窗: 4 hours
Small bowel biopsies will be assessed for markers of innate immune system activation: presence of granulocytes, granulocyte degranulation, products of degranulation, interleukins and cytokines involved in the innate immune system response, inflammatory mediators.
次要结局
- Changes in Mucosal Permeability after Oral Gluten Challenge(Baseline and up to eight hours after gluten or placebo exposure)
- Detection of Gluten Peptides in Urine and Stool(Baseline and up to 72 hours after gluten or placebo exposure)
- Rapid Onset Symptom Development after Gluten Exposure(Baseline and up to 72 hours after gluten or placebo exposure)
研究者
Joseph A. Murray, M.D.
Professor of Medicine
Mayo Clinic