The goal of this prospective interventional study is to evaluate whether the targeted avoidance of a particular food that was diagnosed to be disruptive for the intestinal barrier during confocal laser endomicroscopy (CLE) contributes significantly to stabilizing the intestinal barrier and improving abdominal symptoms, quality of life and disease activity in Crohn's Disease patients with food-related symptoms.
The main questions the study aims to answer are:
* whether a food-induced intestinal barrier disorder in Crohn's disease patients can be detected by endoscopy using confocal laser endomicroscopy (CLE) and a causal relationship with certain foods can be established. * whether a change in diet or a targeted elimination diet can restore the defective integrity of the intestinal barrier detected by CLE. * to examine whether a targeted avoidance of a food that was identified by CLE to trigger intestinal barrier disruption leads to a relevant improvement in symptoms, quality of life and disease activity in patients with Crohn's disease.
Participants will undergo a two-stage nutritional therapy concept based on a two-week inpatient integrative medicinal lifestyle modification program that comprises nutritional therapy, stress management strategies, mind-body medicine, herbal medicine and exercise:
* Initially, participants learn how to employ the comprehensive lifestyle modification concept and receive nutritional training on a mostly vegetarian Mediterranean wholefood diet. * In a first stabilization phase, lasting for 3 months, participants independently apply the taught Mediterranean diet and use strategies from the comprehensive lifestyle modification program. * In a second elimination phase, lasting for another 3 months, participants additionally avoid the particular food that was identified by CLE to induce an intestinal barrier defect.
Crohn's disease patients will:
* initially receive a clinically indicated endoscopy with CLE and food challenge to examine whether a food-induced intestinal barrier disorder is present * return to the clinic for an optional endoscopy with CLE and food challenge after the first (stabilization) phase as well as the second (elimination) phase * answer questionnaires at study start as well as after the first and the second study phase to analyze their quality of life, the severity of their symptoms and their disease activity * give samples of blood, urine, stool and bile fluid as well as intestinal biopsies during regular inpatient sampling at study start as well as after the first and the second study phase * document their intake of food and their symptoms in an App-based diary throughout the study participation
age more than 18 years
Crohn's Disease for at least 6 months (date of initial diagnosis)
with suspected food-induced symptoms or irritable bowel syndrome-like symptoms (fulfils IBS-Rom-IV criteria) for at least 3 months with moderate to severe symptom severity
stable IBD-specific medication dosage for at least 3 months [such as 5-aminosalicylates (5-ASA), thiopurines or biologicals (therapeutic antibodies such as infliximab, adalimumab, vedolizumab, etc.)].
severe flare of Crohn's disease
artificial intestinal outlet
IgE-mediated type 1 allergy to CLE-tested foods (egg white, soy, milk, yeast, wheat)
macroscopic inflammation of the duodenum (detected via endoscopy)
Single group
Two-stage nutritional therapy concept
Other intervention1. Stabilization phase: application of a mostly vegetarian Mediterranean wholefood diet and strategies from a comprehensive lifestyle modification concept. 2. Elimination phase: additional omission diet avoiding the food that was identified by CLE to induce an intestinal barrier defect.
Improvement of the integrity of the duodenal intestinal barrier analyzed by confocal laser endomicroscopy (CLE)
The integrity of the intestinal barrier is tested by CLE during routine Oesophagogastroduodenoscopy. By CLE, the intestinal mucosa and the epithelial lining can be analyzed in vivo with a 1000 x magnification. An intestinal barrier defect can be detected by the leakage of a contrast agent (fluorescein) from the blood vessels through the intestinal epithelial spaces into the intestinal cavity and the shedding of epithelial cells. The impact of 5 foodstuffs (egg white, soy, milk, yeast, wheat) on the intestinal barrier is tested subsequently. The integrity of the intestinal barrier and the reaction to the 5 foodstuffs is tested at baseline as well as after phase 1 (at week 12) and after phase 2 (week 24) in order to identify whether a dietary change or the omission of a particular foodstuff that was identified by baseline CLE to be intestinal barrier disrupting, lead to a relevant improvement in barrier integrity.
Severity of IBS symptoms by IBS-SSS (Irritable Bowel Severity scoring system)
5-item questionnaire with a scale from 0 % (= not at all) to 100 % (= very severe) with a total score ranging from 0 - 500 to evaluate the severity of IBS symptoms. Use of a cut off of IBS-SSS scores to evaluate the severity of IBS: less than 175 for mild IBS, 175-300 for moderate IBS, more than 300 for severe IBS
Severity of IBD-SI (Inflammatory Bowel Disease Symptom Inventory)
The IBD-SI combines items from existing clinician-rated or diary-format inventories. After factor analysis, 38 items were retained on 5 subscales: bowel symptoms, abdominal discomfort, fatigue, bowel complications and systemic complications. A total score as well as subscale scores will be calculated. Higher scores indicate more severe symptoms. Each item is scored between 0 and 4. The total score is calculated by summing the item scores together. Subscale scores are calculated by summing up the scores of particular items (bowel and systemic complications subscales) or by calculating the mean item score across the items of each of these subscales (bowel symptoms, abdominal discomfort, fatigue symptoms subscales).
Severity of HBI (Harvey-Bradshaw-Index)
The disease severity of CD patients is evaluated via a validated questionnaire that is specific for Crohn's Disease (Harvey-Bradshaw-Index): The HBI was designed as a simplified version of the CDAI to enable systematic collection of clinical data on Crohn's disease and is used to assess the degree of illness in individuals with Crohn's disease. The index considers five, exclusively clinical parameters. A specific score is assigned for each parameter. To assess disease activity, the sum score is formed from questions on general condition, abdominal pain, number of unformed bowel movements per day, abdominal resistance and complications. The highest possible sum is 30 points and indicates a severe course of disease. A lower sum than 5 points indicates a clinical remission.
Disease-specific quality of life by IBD-Q (Inflammatory Bowel Disease Questionnaire)
The IBD-Q is the most frequently used questionnaire for disease-specific quality of life in clinical studies on Crohn's disease. It operationalizes quality of life on 4 dimensions (emotional and social impairment as well as bowel-related and systemic symptoms), in addition to a sum score. Answers are recorded on a 7-point Likert scale. High values mean good, low values a reduced quality of life (1=worst score, 7=best score). The total IBD-Q scale ranges from 32 to 224. A score of ≥ 170 can be considered as normal quality of life.
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Universität Duisburg-Essen
Lead sponsor
Heidelberg University
Collaborator
German Crohn's and Colitis Association (DCCV e.V.)
Collaborator
