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

Crohn Disease Clinical Trial

— CD-EDEN  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05606419
• Other study ID #: 605/16-12-2021
• Status: Recruiting
• Phase: N/A
• Start date: January 10, 2023
• Est. completion date: September 2025

Study information

• Verified date: May 2023
• Source: Evangelismos Hospital
• Contact: Konstantina Morogianni, MSc
• Phone: +30 2132045035
• Email: konstantina.morogianni[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Dietary Supplement:
• CDED+PEN
Dietary intervention (Liquid food replacement intervention and specific exclusion diet). Focus on 24 hour diet recalls to asses adherence.
• PEN+usual care
Liquid food replacement intervention and regular diet. Focus on 24 hour diet recalls and FFQ to asses dietary habits.
• CDED+dairy
Dietary intervention (Specific exclusion diet plus early dairy introduction). Focus on 24 hour diet recalls to asses adherence.

Locations

Country	Name	City	State
Greece	Evangelismos General Hospital of Athens	Athens	Attica

Sponsors (2)

Lead Sponsor	Collaborator
Evangelismos Hospital	Agricultural University of Athens

Country where clinical trial is conducted

Greece, 

References & Publications (8)

Bischoff SC, Escher J, Hebuterne X, Klek S, Krznaric Z, Schneider S, Shamir R, Stardelova K, Wierdsma N, Wiskin AE, Forbes A. ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease. Clin Nutr. 2020 Mar;39(3):632-653. doi: 10.1016/j.clnu.2019.11.002. Epub 2020 Jan 13. — View Citation

Gkikas K, Gerasimidis K, Milling S, Ijaz UZ, Hansen R, Russell RK. Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet? Nutrients. 2020 Jul 7;12(7):2018. doi: 10.3390/nu12072018. — View Citation

Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018 Sep;67(9):1726-1738. doi: 10.1136/gutjnl-2017-315866. Epub 2018 May 18. — View Citation

Levine A, Wine E, Assa A, Sigall Boneh R, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J. Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021. Epub 2019 Jun 4. — View Citation

Logan M, Clark CM, Ijaz UZ, Gervais L, Duncan H, Garrick V, Curtis L, Buchanan E, Cardigan T, Armstrong L, Delahunty C, Flynn DM, Barclay AR, Tayler R, McDonald E, Milling S, Hansen RK, Gerasimidis K, Russell RK. The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction. Aliment Pharmacol Ther. 2019 Sep;50(6):664-674. doi: 10.1111/apt.15425. Epub 2019 Jul 25. — View Citation

Wall CL, Day AS, Gearry RB. Use of exclusive enteral nutrition in adults with Crohn's disease: a review. World J Gastroenterol. 2013 Nov 21;19(43):7652-60. doi: 10.3748/wjg.v19.i43.7652. — View Citation

Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2. — View Citation

Yang H, Feng R, Li T, Xu S, Hao X, Qiu Y, Chen M. Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn's disease. Nutr Res. 2020 Sep;81:7-18. doi: 10.1016/j.nutres.2020.06.006. Epub 2020 Jun 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feacal calprotectin	Comparison of faecal calprotectin change between study groups.	Baseline, 6 weeks, 12 weeks
Secondary	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
Secondary	Change in serum CRP	Abnormal/higher values indicate worse outcomes.	Baseline, 6 weeks, 12 weeks
Secondary	Change in serum Albumin	Abnormal values indicate worse outcomes	Baseline, 6 weeks, 12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Weight (kg)	Comparison of body weight between the groups.	Baseline, 6 weeks, 12 weeks
Secondary	Body mass index (BMI) (kg/m^2)	Comparison of Body Mass Index (BMI) (kg/m2) between the groups.	Baseline, 6 weeks, 12 weeks
Secondary	Waist circumference (WC) (cm)	Comparison of WC between groups.	Baseline, 6 weeks, 12 weeks
Secondary	Handgrip strength (kg)	Handgrip strength measured with handgrip strength dynamometer	Baseline, 6 weeks, 12 weeks
Secondary	Fat mass (kg)	Fat mass will be assessed by Bioelectrical Impedance Analysis (BIA)	Baseline, 6 weeks, 12 weeks
Secondary	Fat free mass (FFM) (kg)	Fat free mass will be assessed by Bioelectrical Impedance Analysis (BIA)	Baseline, 6 weeks, 12 weeks
Secondary	Phase angle	Phase angle will be assessed by Bioelectrical Impedance Analysis (BIA)	Baseline, 6 weeks, 12 weeks
Secondary	Neck circumference (cm)	Comparison of neck circumference measured with tape measure between the groups	Baseline, 6 weeks, 12 weeks
Secondary	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
Secondary	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