IBS-Oriented CDED Versus Low FODMAP Diet for Irritable Bowel Syndrome (IBS-CDED)
Open-Label, Randomized Controlled Study to Assess the Efficacy of a Modified Crohn's Disease Exclusion Diet (CDED) Versus Low FODMAP Diet for Managing Non-Constipation Irritable Bowel Syndrome
Background: Irritable Bowel Syndrome (IBS) affects approximately 4.1% of the global population and imposes a significant personal and healthcare burden. Recent evidence highlights the role of low-grade inflammation, impaired intestinal permeability and gut microbiota dysbiosis in the pathophysiology of non-constipated IBS (IBS with predominate diarrhea; IBS-D and mixed type IBS; IBS-M). Most patients report food-related symptom exacerbation, making dietary intervention a cornerstone of treatment. While the low-FODMAP diet (LFD) is widely used to reduce fermentable carbohydrates and alleviate symptoms, it may negatively affect microbial diversity and lacks anti-inflammatory effects. In contrast, the Crohn's Disease Exclusion Diet (CDED), developed for Crohn's disease, has demonstrated the ability to reduce intestinal inflammation, improve barrier function, and promote a favorable microbiota profile. These mechanisms may be relevant and beneficial in IBS, but have yet to be studied in this population.
Objectives: To compare the efficacy of a modified CDED to the LFD for the treatment of non-constipated IBS symptoms, Hypothesis: A modified CDED will be at least as effective as the LFD in alleviating non-constipation IBS symptoms, stool consistency, quality of life, and psychological distress, while demonstrating superior effects on markers of low-grade inflammation, gut microbiota composition, and intestinal permeability.
Methods: This is a single-center, open-label, randomized study to be conducted at the Gastroenterology Department of Sheba Medical Center. 136 adults diagnosed with Rome IV-defined IBS-D or IBS-M and an IBS Symptom Severity Score (IBS-SSS) ≥175 will be randomized 1:1 to receive either a modified CDED or the LFD for 6 weeks. Accounting for a 10% dropout rate, the total sample size will be 150.
Following a 14-day screening period, eligible participants will undergo data collection at baseline, week 3 and week 6. Visit 1 (screening) will be conducted on-site; visits 2-4 will be remote. Participants will complete daily symptom diaries [Bristol Stool Form Scale (BSFS) and GI Visual Analogue Scale (VAS)], and weekly IBS-SSS. Validated questionnaires assessing psychological distress, somatization, extraintestinal symptoms, and quality of life will be administered at each time point.
Stool samples will be collected at baseline, week 3, and week 6. Fecal calprotectin (FC) and α1-Antitrypsin (A1AT) will be analyzed as markers of intestinal inflammation and permeability. Microbiota analysis will be conducted using 16S rRNA gene sequencing, with evaluation of microbial diversity, taxonomic shifts, and associations with clinical and biological outcomes.
Significance: This is the first study to evaluate the modified CDED as a dietary intervention for the treatment of IBS. It may offer a novel, inflammation-targeted alternative treatment for IBS.
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by chronic gastrointestinal symptoms in the absence of structural disease. Increasing evidence suggests that, particularly in non-constipated IBS (IBS-D and IBS-M), impaired intestinal barrier function, gut microbiota dysbiosis, mucosal immune activation, and low-grade inflammation contribute to symptom generation. These findings have shifted the focus of research toward dietary strategies that target underlying biological mechanisms rather than symptom reduction alone.
The low FODMAP diet is currently the most extensively studied dietary intervention for IBS and is recommended by international guidelines. However, despite its effectiveness in reducing gastrointestinal symptoms, concerns remain regarding its potential adverse effects on gut microbial diversity and the lack of evidence for improvement in intestinal inflammation or barrier integrity.
The Crohn's Disease Exclusion Diet (CDED) was originally developed for patients with Crohn's disease and has demonstrated favorable effects on intestinal inflammation, epithelial barrier function, and gut microbiota composition. Because several of these biological pathways are also implicated in IBS pathophysiology, an adapted version of the CDED may provide clinical benefits while simultaneously targeting disease mechanisms that are not addressed by current dietary approaches.
This study will evaluate, for the first time, an IBS-oriented adaptation of the CDED that excludes the enteral formula component used in Crohn's disease. In addition to evaluating clinical efficacy, the study will investigate potential biological mechanisms through serial assessment of fecal inflammatory markers, intestinal permeability markers, and gut microbiota composition. By integrating clinical, psychological, and biological outcomes, the study aims to determine whether this dietary intervention represents a mechanism-based alternative to the current dietary standard of care for patients with non-constipated IBS.
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Keren Hod, RD PhD
- Номер телефона: +972-53-2214380
- Электронная почта: kerenho@ariel.ac.il
Учебное резервное копирование контактов
- Имя: Tal Engel, MD
- Номер телефона: +972-52-5752211
- Электронная почта: talengel@gmail.com
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
Inclusion Criteria:
- Adults, men, and women (≥18 years) are diagnosed with IBS-D or IBS-M according to Rome IV criteria.
- Moderate-to-severe symptoms (IBS-SSS score ≥175).
- Stable use of any IBS-related medications for ≥6 weeks before study enrollment, except for antibiotics
Exclusion Criteria:
- Coexisting GI diseases [e.g., Crohn's disease, ulcerative colitis, SIBO, celiac disease [positive transglutaminase (TTG) serology].
- Disease that could explain or influence symptoms or GI function, including diabetes, thyroid disease [abnormal Thyroid-Stimulating Hormone (TSH)], and bariatric surgery.
- Recent intestinal resection.
- Pregnancy or breastfeeding.
- Known food allergies.
- Current active eating disorder
- Participants already following a restrictive diet, including diets that overlap with the interventions in this study, will be excluded to prevent confounding effects on gut microbiota composition and gastrointestinal symptoms, and to ensure consistent baseline conditions. However, individuals who have discontinued such diets at least two to four weeks prior to enrollment may be eligible, allowing for a sufficient dietary washout period to minimize residual effects on the gut microbiota.
- Currently under obesity management medication treatment.
- Vegans
- Use of antibiotics within the 4 weeks prior to enrollment or during the study period.
- Abnormal hemoglobin levels (for women<11.5 gr/dl, for men<13 gr/dl)29
- Baseline CRP≥5
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Modified Crohn's Disease Exclusion Diet (CDED)
Participants randomized to this arm will follow a modified Crohn's Disease Exclusion Diet (CDED) adapted for patients with irritable bowel syndrome.
The intervention excludes the enteral formula used in the original CDED protocol and is delivered for 6 weeks with individualized dietary counseling.
|
Participants will follow a modified Crohn's Disease Exclusion Diet (CDED) adapted for patients with irritable bowel syndrome.
The intervention excludes the enteral formula used in the original CDED protocol and is delivered for 6 weeks with individualized dietary counseling.
|
|
Активный компаратор: Low FODMAP Diet
Participants randomized to this arm will follow a standard low FODMAP diet for 6 weeks with individualized dietary counseling.
|
Participants will follow a standard low FODMAP diet for 6 weeks with individualized dietary counseling.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Proportion of participants achieving a clinically meaningful response (≥50-point reduction in IBS Symptom Severity Score [IBS-SSS])
Временное ограничение: Baseline and Week 6
|
The primary efficacy outcome is the proportion of participants achieving a clinically meaningful response, defined as a reduction of at least 50 points from baseline in the IBS Symptom Severity Score (IBS-SSS) after 6 weeks of treatment.
The IBS-SSS is a validated questionnaire ranging from 0 to 500, with higher scores indicating greater symptom severity.
|
Baseline and Week 6
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Proportion of participants achieving a ≥100-point reduction in IBS Symptom Severity Score (IBS-SSS)
Временное ограничение: Baseline and Week 6
|
Proportion of participants achieving a reduction of at least 100 points from baseline in the IBS Symptom Severity Score (IBS-SSS) after 6 weeks of treatment.
|
Baseline and Week 6
|
|
Proportion of participants achieving a ≥50% reduction in IBS Symptom Severity Score (IBS-SSS)
Временное ограничение: Baseline and Week 6
|
Proportion of participants achieving a reduction of at least 50% from baseline in the IBS Symptom Severity Score (IBS-SSS) after 6 weeks of treatment.
|
Baseline and Week 6
|
|
Change from baseline in IBS Symptom Severity Score (IBS-SSS)
Временное ограничение: Baseline, Week 3, and Week 6
|
Absolute and percentage change from baseline in the IBS Symptom Severity Score (IBS-SSS).
Scores range from 0 to 500, with higher scores indicating greater symptom severity.
|
Baseline, Week 3, and Week 6
|
|
Change from baseline in gastrointestinal symptom severity (Visual Analog Scale)
Временное ограничение: Baseline, Week 3, and Week 6
|
Absolute and percentage change from baseline in gastrointestinal symptom severity assessed using a Visual Analog Scale (VAS), with higher scores indicating greater symptom severity.
|
Baseline, Week 3, and Week 6
|
|
Change in quality of life
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in IBS-specific quality of life measured using the IBS-Quality of Life questionnaire (IBS-QOL).
Scores range from 0 to 100, with higher scores indicating better quality of life.
|
Baseline, Week 3, and Week 6
|
|
Change in psychological distress
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in psychological distress assessed using the Hospital Anxiety and Depression Scale (HADS), a validated 14-item questionnaire consisting of two 7-item subscales assessing anxiety (HADS-A) and depression (HADS-D).
Each subscale ranges from 0 to 21, with higher scores indicating greater symptom severity.
Total HADS score ranges from 0 to 42, with higher scores indicating greater overall psychological distress.
|
Baseline, Week 3, and Week 6
|
|
Change in extraintestinal symptoms
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in extraintestinal symptom burden assessed using a modified version of the Patient Health Questionnaire (PHQ-15), including 12 non-gastrointestinal items after exclusion of the three gastrointestinal symptom items (abdominal pain, constipation/diarrhea, and nausea/gas/indigestion).
Each item is scored from 0 to 2, with higher scores indicating greater extraintestinal symptom burden.
|
Baseline, Week 3, and Week 6
|
|
Change in intestinal permeability measured by fecal α1-antitrypsin (A1AT)
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in fecal α1-antitrypsin concentration, a biomarker of intestinal permeability.
|
Baseline, Week 3, and Week 6
|
|
Change in fecal calprotectin concentration
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in fecal calprotectin concentration as a marker of intestinal inflammation.
|
Baseline, Week 3, and Week 6
|
|
Change in gut microbiota composition
Временное ограничение: Baseline, Week 3, and Week 6
|
Change from baseline in gut microbiota composition and diversity assessed by 16S rRNA gene sequencing.
|
Baseline, Week 3, and Week 6
|
|
Participants' experiences with the dietary intervention
Временное ограничение: Follow up: after completion of the 6-week intervention
|
Participants' perceptions, barriers, facilitators, and overall experiences with the assigned dietary intervention assessed through structured qualitative interviews.
|
Follow up: after completion of the 6-week intervention
|
Соавторы и исследователи
Спонсор
Следователи
- Учебный стул: Keren Hod, RD PhD, Ariel University
Публикации и полезные ссылки
Полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Патологические процессы
- Генетические заболевания, врожденные
- Кишечные заболевания
- Заболевания дыхательных путей
- Заболевания пищеварительной системы
- Желудочно-кишечные заболевания
- Легочные заболевания
- Заболевания печени
- Заболевания толстой кишки
- Болезни толстой кишки, функциональные
- Подкожная эмфизема
- Эмфизема
- Врожденные, наследственные и неонатальные заболевания и аномалии
- Патологические состояния, признаки и симптомы
- Синдром раздраженного кишечника
- Альфа 1-антитрипсин дефицит
- Диета, еда и питание
- Физиологические явления
- Пищевые физиологические явления
- Диета
- Элиминация диеты
- Диета FODMAP
Другие идентификационные номера исследования
- 2495-25-SMC
- 0009547 (Другой номер гранта/финансирования: Ministry of Innovation, Science and Technology, Israel)
- 202540302 (Другой идентификатор: Israel Ministry of Health)
Планирование данных отдельных участников (IPD)
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