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

Sponsor

Evangelismos Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05606419

Collaborator

Agricultural University of Athens (Other)

120

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to evaluate a novel diet for adult Crohn's disease patients (The Crohn's Disease Exclusion Diet - CDED) plus partial enteral nutrition. Half of the patients in this study will receive the CDED combined with partial enteral nutrition (PEN) and the other half will receive PEN along with the usual nutritional care. Moreover, the investigators wish to challenge patients in remission with a low dose exposure to dairy products, that were eliminated from the CDED, to examine if that exposure is well tolerated.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Dietary Supplement: CDED+PEN+dairy products Dietary Supplement: PEN+usual care	N/A

Detailed Description

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 in remission with a low dose exposure to dairy products, to assess tolerability, prospecting for the development of a personalized remission maintenance diet 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 or inactive CD.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients in remission will follow the first stage diet (CDED+PEN) for 4 weeks and will continue with CDED + PEN + dairy products for another 4 weeks. Patients with active disease will follow the first stage diet (CDED + PEN) for 6 weeks and then, the responders will continue with adding the dairy product for 4 more 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.Patients in remission will follow the first stage diet (CDED+PEN) for 4 weeks and will continue with CDED + PEN + dairy products for another 4 weeks. Patients with active disease will follow the first stage diet (CDED + PEN) for 6 weeks and then, the responders will continue with adding the dairy product for 4 more 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)

Primary Purpose:

Supportive Care

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1-Remission Crohn's Disease Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN)+dairy products: Patients with asymptomatic disease will follow the first stage diet (CDED+50%PEN) for 4 weeks and will continue with CDED + 25%PEN + dairy products for another 4 weeks. Total duration: 8 weeks.	Dietary Supplement: CDED+PEN+dairy products Dietary intervention (Liquid food replacement intervention and specific exclusion diet with gradual re-introduction of dairy products). Focus on 24 hour diet recalls to asses adherence.
Active Comparator: Group 2 - Remission Partial Enteral Nutrition (PEN) + usual nutritional care: Patients with asymptomatic disease 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 4 weeks. During the second 4 weeks, PEN will cover the 25% of the total energy requirements.Total duration: 8 weeks	Dietary Supplement: PEN+usual care Liquid food replacement intervention and regular diet. Focus on 24 hour diet recalls and FFQ to asses dietary habits.
Experimental: Group 1 - Active Disease Crohn's Disease Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN)+dairy products: Patients with active disease will follow the first stage diet (CDED + 50%PEN) for 6 week and then, the responders will continue with adding the advised dairy products for 4 more weeks (CDED+25%PEN+dairy products).	Dietary Supplement: CDED+PEN+dairy products Dietary intervention (Liquid food replacement intervention and specific exclusion diet with gradual re-introduction of dairy products). Focus on 24 hour diet recalls to asses adherence.
Active Comparator: Group 2 - Active Disease Partial Enteral Nutrition (PEN) + usual nutritional care: Patients with symptomatic disease will be given PEN plus the usual advice for a low residue diet. PEN will cover the 50% of total energy requirements for the first 6 weeks. During the next 4 weeks, PEN will cover the 25% of the total energy requirements.Total duration: 10 weeks	Dietary Supplement: PEN+usual care Liquid food replacement intervention and regular diet. Focus on 24 hour diet recalls and FFQ to asses dietary habits.

Outcome Measures

Primary Outcome Measures

Feacal calprotectin [Baseline, 4 weeks, 8 weeks (Baseline, 6 weeks, 10 weeks for patients entering the study with active disease)]
Number of participants with 20% or more improvement in faecal calprotectin

Secondary Outcome Measures

Clinical response-Harvey-Bradshaw Index (HBI) [Baseline, week 4, week 8 (Baseline, week 6, week 10 for patients entering the study with active disease)]
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
Change in serum CRP [Baseline, week 4, week 8 (Baseline, week 6, week 10 for patients entering the study with active disease)]
Abnormal/higher values indicate worse outcomes.
Change in serum Albumin [Baseline, week 4, week 8 (Baseline, week 6, week 10 for patients entering the study with active disease)]
Abnormal values indicate worse outcomes. Abnormal values indicate worse outcomes. Abnormal values indicate worse outcomes
Bowel symptoms improvement [Baseline, 8 weeks (Baseline, 6 weeks, 10 weeks for patients entering the study with active disease)]
Percent of patients who reported improvement in bowel symptoms, assessed by the validated IBDQ (bowel symptoms domain: 10 questions)
Health Related Quality of Life (HR-QoL) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
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.
Patient's tolerance to the diet [Baseline, week 4, week 8 (Baseline, week 6, week 10 for patients entering the study with active disease)]
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.
Weight (kg) [Baseline, week 4, week 8 (Baseline, week 6, week 10 for patients entering the study with active disease)]
Comparison of body weight between the groups.
Body mass index (BMI) (kg/m^2) [Baseline, week 4, week 8 (Baseline, 6 weeks, 10 weeks for patients entering the study with active disease)]
Comparison of Body Mass Index (BMI) (kg/m2) between the groups.
Waist circumference (WC) (cm) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Comparison of WC between groups.
Handgrip strength (kg) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Handgrip strength measured with handgrip strength dynamometer
Fat mass (kg) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Fat mass will be assessed by Bioelectrical Impedance Analysis (BIA)
Fat free mass (FFM) (kg) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Fat free mass will be assessed by Bioelectrical Impedance Analysis (BIA)
Phase angle [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Phase angle will be assessed by Bioelectrical Impedance Analysis (BIA)
Neck circumference (cm) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Comparison of neck circumference measured with tape measure between the groups
Mid arm circumference (MAC) (cm) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Measured with tape measure to assess Mid-arm muscle circumference (MAMC) (for estimating FFM, when BIA is not feasible)
Triceps Skinfold (TSF) (mm) [Baseline, week 8 (Baseline, week 10 for patients entering the study with active disease)]
Measured with a skinfold caliper to assess Mid-arm muscle circumference (MAMC) for estimating FFM, when BIA in not feasible)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must have an established diagnosis of CD
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Evangelismos Hospital
Agricultural University of Athens

Investigators

Principal Investigator: Dimitrios Karayiannis, Dr., Evangelismos General Hospital of Athens
Study Director: Kalliopi Anna Poulia, Dr., Agricultural University of Athens
Study Chair: Gerasimos Mantzaris, Dr., Evangelismos General Hospital of Athens