Gynaecological Disorders in Patients With Not-celiac Wheat Sensitivity

University of Palermo3 个研究点分布在 1 个国家目标入组 500 人开始时间: 2001年1月1日最近更新: 2026年4月14日

适应症

干预措施

试验速览

阶段: 不适用
状态: 已完成
发起方: University of Palermo
入组人数: 500
试验地点: 3
主要终点: Gynaecological disorders in NCWS female patients at baseline

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

In the last few years, a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the investigators suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and very different extra-intestinal and systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays, there no data about a possible relationship between gynaecological disorders and food ingestion and food allergy/intolerance. Therefore, the aims of the present study are to investigate 1) the prevalence and characteristics of gynaecological disorders in NCWS patients compared to healthy, CD and irritable bowel syndrome (IBS) controls, 2) the modification of such disorders in NCWS patients after a gluten (wheat)-free diet, and 3) whether cytological alterations could be identified on samples taken during Papanicolaou (PAP) tests performed in NCWS patients with uro-gynecological disorders on strict WFD and after a 7-day open challenge with wheat.

详细描述

In the last few years, a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the investigators suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. Other areas of doubt in NCWS regard its pathogenesis, while some papers reported intestinal immunologic activation, others linked NCWS to the dietary short chain carbohydrate (fermentable oligo-di-monosaccharides and polyols, FODMAPs) load. The investigators recently demonstrated that higher proportions of patients with NCWS develop autoimmune disorders, are antinuclear antibodies (ANA) positive, and show DQ2/DQ8 haplotypes compared with patients with IBS, supporting an immunologic involvement in NCWS. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and very different extra-intestinal and systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays, there no data about a possible relationship between gynaecological disorders (i.e. menstrual cycle alterations, vaginitis, recurrent vulvovaginitis, recurrent cystitis, chronic pelvic pain, recurrent pregnancy loss, infertility) and food ingestion and food allergy/intolerance. Therefore, the aims of the present study are to investigate 1) the prevalence and characteristics of gynaecological disorders in NCWS patients compared to healthy, CD and IBS controls, 2) the modification of such disorders in NCWS patients after a gluten (wheat)-free diet, and 3) whether cytological alterations could be identified on samples taken during Papanicolaou (PAP) tests performed in NCWS patients with uro-gynecological disorders on strict WFD and after a 7-day open challenge with wheat.

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: None

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

•To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet the following criteria:
•age ≥18 years and ≤65 years;
•negative serum assays for celiac disease: anti-deamidated gliadin peptide (anti-DGP) Ig (Immunoglobulin)A and IgG antibodies, anti-tissue transglutaminase (anti-tTG) IgA and IgG antibodies, and anti-endomysium (anti-EMA) IgA antibodies;
•absence of duodenal villous atrophy, documented in all the patients carrying the DQ2 and/or DQ8 Human Leukocyte Antigens (HLA) haplotypes, evaluated during the ingestion of at least 100g of bread and/or pasta every day for at least 45 days;
•exclusion of IgE-mediated wheat allergy, documented by a negative skin prick-test and/or serum dosage of IgE specific for wheat, gluten and gliadin;
•complete resolution of symptoms after a strict standard elimination diet (oligoantigenic diet, free of wheat, cow's milk, eggs, tomatoes, chocolate, and other foods self-reported by patient as cause of symptoms) continued for at least 4 weeks, followed by the recurrence of symptoms after double-blind placebo-controlled wheat challenge or open challenges for the others self-reported foods;
•To diagnose CD the standard criteria will be adopted. All the patients will meet the following criteria:
•positive serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies
•presence of intestinal villous atrophy;
•To diagnose IBS the standard Rome II (for retrospective patients) and Rome III (for prospective patients) Criteria will be adopted. None of these subjects improved on an elimination diet without wheat, cow's milk, egg, tomato, or chocolate.

排除标准

•For NCWS diagnosis it will be evaluated the following exclusion criteria:
•self-elimination of wheat from the diet and refusal to reintroduce it for a diagnostic purpose, before entering in to the study;
•treatment with corticosteroids and non steroidal anti-inflammatory (FANS) drugs during the 2 weeks before the duodenal biopsies;
•EMA positivity in the culture medium of duodenal biopsies (EMA biopsy), even with a normal villo/crypt ratio in the mucosa;
•pregnancy or breastfeeding;
•alcohol and/or drug abuse;
•chronic inflammatory bowel disease or other intestinal organic disease; nervous system disease or major psychiatric disorders; infectious diseases; immunological deficits and physical impairments; 7) diagnosis of uro-gynecological organic diseases (uro-genital infections, endometriosis, neoplasms, etc.), confirmed by an uro-gynecologist both before the diagnosis of NCWS and during the follow-up period.
•Additional specific inclusion/exclusion criteria for NCWS patients were used in this study: 1) female patient complaining of uro-gynecological disorders; 2) at least one uro-gynecological visit, including an uro-gynecological ultrasound and microbiological tests, that excluded uro-gynecological organic diseases within 6 months before the recruitment in the study; 3) follow-up period of at least 12 months after the initial diagnosis of NCWS and at least 2 outpatient, every 6 months, visits during the follow-up; 4) strict adherence to WFD 12 months after NCWS diagnosis.
•Healthy controls had to respect the following inclusion criteria: 1) female gender; 2) age ≥18 years and ≤65 years; 3) negative serology for anti- Deamidated Gliadin Peptide (DGP) IgA and IgG antibodies, anti-tissue TransGlutaminase (tTG) IgA and IgG antibodies; 4) absence of self-reported symptoms related to wheat intake; 5) at least one uro-gynecological visit, including an uro-gynecological ultrasound and microbiological tests, that excluded uro-gynecological organic diseases within 6 months before the recruitment in the study.
•Additional exclusion criteria for both NCWS patients and healthy controls were: 1) use of drugs potentially causes of the uro-gynecological disorders; 2) diagnosis of uro-gynecological organic diseases (uro-genital infections, endometriosis, neoplasms, etc.), confirmed by an uro-gynecologist; 3) previous surgical interventions on the uro-genital system; 4) absence of signed informed consent form.

研究组 & 干预措施

2. CD retrospective control patients

Active Comparator

To compare the presence and characteristics of gynaecological disorders in NCWS female patients, a control group of CD female patients had been randomly chosen by a computer-generated method from female patients diagnosed during the same period (2001-2024) and in the same centers, and age- (+2 years) matched with the NCWS female patients. Similar to NCWS patients, also this control group was asked for gynaecological disorders and the answers reported in the patients clinical charts. All the patients will be evaluated at baseline (i.e. at diagnosis) and after at least a 6-months period of gluten-free diet.