The Crohn's Disease Exclusion Diet With Early Dairy Introduction Plus Partial Enteral Nutrition for Crohn's Disease

Study Overview
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Brief Summary
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This study aims to evaluate a novel diet for adult Crohn's disease patients (The Crohn's Disease Exclusion Diet - CDED). Some of the patients in this study will receive the CDED combined with partial enteral nutrition (PEN), the other group will receive PEN along with the usual nutritional care and the third group will follow the CDED with early introduction of dairy products, that were eliminated from the initial CDED protocol.

Detailed Description
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Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease that has a significant impact on patients' quality of life and is of increased incidence worldwide. The disease aetiology is complex and not fully understood. Accumulated data indicate that environmental factors, including diet, might play a key role in the pathogenesis and inflammation, through mechanisms involving gut dysbiosis, in genetically susceptible people. Epidemiological data suggest that a Mediterranean dietary pattern is associated with decreased risk for CD, whereas a Western diet, rich in animal fat, processed foods and food additives, seems to be linked with an increased disease risk. Exclusive Enteral Nutrition (EEN) is the only well-established dietary therapy in CD and is used as the first line therapy for the induction of remission in mild to moderate pediatric CD. Evidence according to EEN efficacy in adults is not consistent, which could partly be explained by the compliance difficulty. It is of interest, that feacal inflammation increases rapidly after food re-introduction following EEN in children. Partial enteral nutrition (PEN) has been shown to be beneficial in maintaining remission, but poor compliance due to low formula palatability and patients' fatigue remains an important barrier in the clinical practice. Moreover, PEN is inferior to EEN in inducing remission. Crohn's Disease Exclusion Diet (CDED), which eliminates specific dietary components hypothesized to induce dysbiosis, appears to be effective in inducing and maintaining remission both in pediatric and adult populations. In parallel, patients express a strong interest in ways to manage their disease through diet, so the establishment of a palatable and as flexible as possible dietary pattern, not merely for inducing remission, but also as a feasible maintenance strategy is one of the main priorities in CD research at present. Therefore, the aim of this study is to explore the effectiveness of the CDED and PEN in both inducing and maintaining remission of CD in adults. The investigators also wish to challenge patients with an early exposure to dairy products, to assess tolerability, prospecting for the development of a more flexible dietary approach based on the CDED principles. The investigators aim to assess the intervention effect on CD activity, based on routinely used clinical indices, blood and faecal inflammatory biomarkers (CRP, FC), health-related quality of life, nutritional status and dietary intake, in patients with mildly active CD.

Official Title
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The Crohn's Disease Exclusion Diet With Early Dairy Introduction Plus Partial Enteral Nutrition (CD-EDEN) in Adult Patients With Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Dietary Supplement: CDED+PEN
* Dietary Supplement: PEN+usual care
* Dietary Supplement: CDED+dairy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have an established diagnosis of CD Participants must be in active disease, defined by either the confirmed inflammation at screening as CRP >5 mg/L, FC >200 mg/g, or presence of inflammation on endoscopy in the 3 months before screening based on retrospective review of procedure reports by the local investigator and the clinician's assessment Individuals able to give informed consent and willingness to participate Exclusion Criteria: Age < 18 years old Previous extensive bowel resection Reported pregnancy or lactation Current stoma Current stenosis or abscess Clinically significant stricture Introduction of or change in dose of drug therapy within the past 8 weeks Comorbidities including diabetes or coeliac disease, or other concomitant serious comorbidity e.g. significant psychiatric, hepatic, renal, endocrine, respiratory, neurological, cardiovascular, neoplastic or other autoimmune disease Food allergies or intolerances, which do not permit participation in the study Any proven current infection such as positive stool cultures or positive tests for parasites or C. difficile. Stool tests are mandatory only if diarrhea is present.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with active disease will follow either the CDED diet protocol (CDED + PEN), the usual nutritional care plus PEN, or the CDED diet with dairy products included, for 12 weeks. All participants will attend study visits at the beginning, in the middle and at end of the trials, at which points questionnaires will be completed and samples will be collected.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDED + PEN<br>Crohn's Disease Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN): Patients will follow the first phase diet (CDED+50%PEN) for 6 weeks and will continue with CDED phase 2 + 25%PEN for another 6 weeks. Total duration: 12 weeks. | Dietary Supplement: CDED+PEN<br>* Dietary intervention (Liquid food replacement intervention and specific exclusion diet). Focus on 24 hour diet recalls to asses adherence.<br>|
| Active Comparator: Usual Nutritional Care + PEN<br>Partial Enteral Nutrition (PEN) + usual nutritional care: Patients will be given PEN plus the usual advice for a healthy dietary pattern. PEN will cover the 50% of total energy requirements for the first 6 weeks. During the second 6 weeks, PEN will cover the 25% of the total energy requirements.Total duration: 12 weeks | Dietary Supplement: PEN+usual care<br>* Liquid food replacement intervention and regular diet. Focus on 24 hour diet recalls and FFQ to asses dietary habits.<br>|
| Active Comparator: CDED + Dairy<br>Crohn's Disease Exclusion Diet (CDED) + dairy products: Patients will follow the first phase diet CDED + 50% of their energy requirements covered by dairy products for 6 week and then will continue with the CDED phase 2 diet + 25% dairy products. | Dietary Supplement: CDED+dairy<br>* Dietary intervention (Specific exclusion diet plus early dairy introduction). Focus on 24 hour diet recalls to asses adherence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feacal calprotectin | Comparison of faecal calprotectin change between study groups. | Baseline, 6 weeks, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response-Harvey-Bradshaw Index (HBI) | Higher HBI scores indicate worse outcomes. Clinical response is defined as baseline HBI score decrease of ≥ 3, and clinical remission is defined as score <5 | Baseline, 6 weeks, 12 weeks | 
| Change in serum CRP | Abnormal/higher values indicate worse outcomes. | Baseline, 6 weeks, 12 weeks | 
| Change in serum Albumin | Abnormal values indicate worse outcomes | Baseline, 6 weeks, 12 weeks | 
| Bowel symptoms improvement | Percent of patients who reported improvement in bowel symptoms, assessed by the validated IBDQ (bowel symptoms domain: 10 questions) | Baseline, 6 weeks, 12 weeks | 
| Health Related Quality of Life (HR-QoL) | HR-QoL defined by the self-administered Inflammatory Bowel Disease questionnaire (IBDQ) score. Higher IBDQ scores indicate better outcomes. Clinical response defined as increase ≥16 points. | Baseline, 6 weeks, 12 weeks | 
| Patient's tolerance to the diet | Intolerance: patient's refusal to continue diet (based on reporting and the 24 hour recalls); Adherence will be assessed based on the modified Medication Adherence Report Scale (MARS) questionnaire; The modified MARS questionnaire rates how closely patients adhere to the diet. A score of 1-5 indicates that the patient is not adherent; a score of 6-9 indicates that the patient is adherent. | Baseline, 6 weeks, 12 weeks | 
| Weight (kg) | Comparison of body weight between the groups. | Baseline, 6 weeks, 12 weeks | 
| Body mass index (BMI) (kg/m^2) | Comparison of Body Mass Index (BMI) (kg/m2) between the groups. | Baseline, 6 weeks, 12 weeks | 
| Waist circumference (WC) (cm) | Comparison of WC between groups. | Baseline, 6 weeks, 12 weeks | 
| Handgrip strength (kg) | Handgrip strength measured with handgrip strength dynamometer | Baseline, 6 weeks, 12 weeks | 
| Fat mass (kg) | Fat mass will be assessed by Bioelectrical Impedance Analysis (BIA) | Baseline, 6 weeks, 12 weeks | 
| Fat free mass (FFM) (kg) | Fat free mass will be assessed by Bioelectrical Impedance Analysis (BIA) | Baseline, 6 weeks, 12 weeks | 
| Phase angle | Phase angle will be assessed by Bioelectrical Impedance Analysis (BIA) | Baseline, 6 weeks, 12 weeks | 
| Neck circumference (cm) | Comparison of neck circumference measured with tape measure between the groups | Baseline, 6 weeks, 12 weeks | 
| Mid arm circumference (MAC) (cm) | Measured with tape measure to assess Mid-arm muscle circumference (MAMC) (for estimating FFM, when BIA is not feasible) | Baseline, 6 weeks, 12 weeks | 
| Triceps Skinfold (TSF) (mm) | Measured with a skinfold caliper to assess Mid-arm muscle circumference (MAMC) for estimating FFM, when BIA in not feasible) | Baseline, 6 weeks, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Diseases, Diet therapy, Crohn's Disease, Enteral Nutrition, Partial Enteral Nutrition, Gastrointestinal Diseases