Dose-finding Gluten Challenge Trial in Nonceliac Gluten-sensitivity
關鍵詞
抽象
描述
The Investigators will consecutively enroll adult patients referred to outpatients' Clinics of 21 Centres because of persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten. In their clinical management patients in gluten-containing diet since at least two months will undergo ad hoc tests including serum determination of IgA anti-tissue transglutaminase and anti-endomysial antibodies, IgG anti-gliadin antibodies (AGA), total IgA and IgE, wheat-specific IgE, upper endoscopy with collection of multiple duodenal biopsies, HLA genotyping, fecal calprotectin and lactose breath test. The Investigators will investigate serum AGA IgG since they have been detected in some patients with "suspected" nonceliac gluten sensitivity. Patients with celiac disease, wheat allergy, intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols, lactose intolerance, Helicobacter pylori infection, giardiasis, inflammatory bowel disease, cirrhosis, excessive alcohol intake, intake of nonsteroidal anti-inflammatory agents, use of systemic immunosuppressant medication, poorly controlled psychiatric disease, pregnancy and those unable to give written informed consent will be excluded. The Investigators will also recruit as control group 420 age- and sex-matched healthy volunteers, undergoing IgG AGA and all negative for anti-tissue transglutaminase antibodies. Healthy volunteers will not be affected by any comorbidity and food intolerance.
Each Centre will enroll 20 patients with suspected nonceliac gluten sensitivity and 20 healthy volunteers. Recruitment of patients and, at greater extent, healthy volunteers should not be an issue as the 21 Centres involved in this trial are well-known for diagnosis and treatment of gluten-related disorders. The Investigators will consider drop-outs from the study all the patients who will fail to attend even a single appointment or test in the trial. Moreover, compliance with the study treatment will be assessed by unused capsule counts at T2 and T4. Compliance with the gluten-free diet at each time point will be assessed through a validated questionnaire. To exclude the possibility of patients being able to discriminate between gluten capsules and placebo capsules, we preliminarily tested capsule recognition in a group of 20 healthy volunteers. On two different days, healthy volunteers were asked to take capsules and then clearly state if the capsules contained gluten or not. Healthy volunteers were not able to differentiate the appearance and taste of gluten capsules from those of placebo capsules. Assuming a within-patient comparison and a SD of the overall score of 40, 70 subjects per arm would be needed in order to achieve a power of 80%, at a 2-sided 5% significance level, if the true difference is 15.
日期
| 最後驗證: | 07/31/2018 |
| 首次提交: | 06/12/2017 |
| 提交的預估入學人數: | 06/12/2017 |
| 首次發布: | 06/14/2017 |
| 上次提交的更新: | 08/08/2018 |
| 最近更新發布: | 08/09/2018 |
| 實際學習開始日期: | 06/12/2017 |
| 預計主要完成日期: | 06/12/2019 |
| 預計完成日期: | 12/12/2020 |
狀況或疾病
干預/治療
Diagnostic Test: Gluten or placebo capsules
相
手臂組
| 臂 | 干預/治療 |
|---|---|
| Active Comparator: 1A - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 14 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 8.4 grams for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Active Comparator: 1B - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Active Comparator: 1C - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2C - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2B - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 10 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2A - NCGS Seventy subjects with nonceliac gluten sensitivity will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 8.4 grams for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Active Comparator: 1A - HV Seventy healthy volunteers will be given 14 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 8.4 grams for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Active Comparator: 1B - HV Seventy healthy volunteers will be given 10 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 6.0 grams for five days. In order to maintain the double-blind, patients will be also given 4 capsules of placebo (rice starch) per day. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Active Comparator: 1C - HV Seventy healthy volunteers will be given 7 gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2C- HV Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2B - HV Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 7 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 4.2 grams for five days. In order to maintain the double-blind, patients will be also given 7 capsules of placebo (rice starch) per day. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. | |
| Placebo Comparator: 2A - HV Seventy healthy volunteers will be given 14 daily gastrosoluble capsules containing placebo (rice starch) for five days. At the end of the first five day-long treatment, subjects will continue only their wash-out from gluten for two weeks, without taking any capsule. At T3, individuals will be given 14 daily gastrosoluble capsules containing purified wheat gluten corresponding to a daily gluten intake of 8.4 grams for five days. In both first and second five day-long treatment the 14 capsules will be ingested in no more than two times using a glass of water over the day. |
資格標準
| 有資格學習的年齡 | 18 Years 至 18 Years |
| 有資格學習的性別 | All |
| 接受健康志願者 | 是 |
| 標準 | Inclusion Criteria: - persistence of relevant intestinal and extraintestinal symptoms believed by them to be caused by the ingestion of food containing even low doses of gluten Exclusion Criteria: - celiac disease - wheat allergy - intolerance to further food source of fermentable oligo- and disaccharides, monosaccharides and polyols - lactose intolerance - Helicobacter pylori infection - giardiasis - inflammatory bowel disease - cirrhosis - excessive alcohol intake - intake of nonsteroidal anti-inflammatory agents - use of systemic immunosuppressant medication - poorly controlled psychiatric disease - pregnancy - patients unable to give written informed consent will be excluded |
結果
主要結果指標
1. Change in delta overall (intestinal plus extraintestinal) score in nonceliac gluten sensitivity [18 months]
次要成果指標
1. The change in individual symptom scores between the 5-day treatment with gluten and the 5-day treatment with placebo [18 months]
2. The identification of patients with true nonceliac gluten sensitivity [18 months]
3. Laboratory parameters as predictors of true nonceliac gluten sensitivity [24 months]
4. Change in delta overall (intestinal plus extraintestinal) score between the highest daily intake of gluten (8.4 grams) and the lowest ones (either 6.0 or 4.2 grams) in healthy volunteers [24 months]
