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The modified-Exclusive Enteral Nutrition (mEEN) is an open label randomized controlled trial in mild to severe Crohn's Disease patients. The purpose of this study is to determine whether induction of remission and maintenance of remission can be achieved with a new dietary strategy that involves only 2 weeks of Exclusive Enteral Nutrition (EEN) with Modulen and 12 weeks of an exclusion diet involving selected table foods. This novel approach will be compared to the gold standard dietary regime involving 8 weeks of EEN.
Rational: Exclusive enteral nutrition (EEN) is an established but difficult to perform method for induction of remission and cannot be used for maintenance of remission. It entails drinking only liquid formula for 8 weeks. Refusal to use or to adhere to this therapy is not uncommon and leads to use of other non- dietary strategies in children including steroids and immunosuppression. The Crohn's Disease Exclusion Diet (CDED) with partial enteral nutrition has been shown to be effective for children with mild to moderate disease. The investigators have developed a maintenance strategy using the CDED.
Objectives: To prove that induction of remission and maintenance of remission can be achieved with a new dietary strategy that involves only 2 weeks of EEN with Modulen and 12 weeks of an exclusion diet involving selected table foods.
Methods: Open label randomized controlled pilot trial comparing two weeks of EEN followed by the CDED and Partial Enteral Nutrition (PEN), to 8 weeks of EEN followed by PEN with free diet. The study will include a control group of healthy children for microbiome studies.
Population: Age 8-18 years with mild to severe active Crohn's disease defined as 15≤Pediatric Crohn's Disease Activity Index (PCDAI)<47.5.
Time frame: The induction of remission phase will last 8 weeks followed by maintenance phase for a period of 24 weeks.
Expected outcomes and significance: If this method proves to be equivalent to EEN, the duration of use of EEN will be only two weeks, allowing more patients access to dietary therapy. More importantly, this study will also evaluate two maintenance strategies and will be the first to evaluate re-biosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | Modified Exclusive Enteral Nutrition including two weeks of Exclusive Enteral Nutrition (EEN) using Modulen followed by Partial Enteral Nutrition (PEN) along with the Crohn's Disease Exclusion Diet (CDED) phases 2 & 3 for 24 weeks |
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| Group 2 | Active Comparator | Standard Exclusive Enteral Nutrition for 8 weeks using Modulen, followed by free diet with gradual reduction of Modulen to 25% of energy needs by week 24. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Modified Exclusive Enteral Nutrition | Other | Two weeks of Exclusive Enteral Nutrition with Modulen |
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| Measure | Description | Time Frame |
|---|---|---|
| ITT, steroid free Clinical remission (defined as Pediatric Crohn's Disease Activity Index (PCDAI)<10) at week 14 | Sustained remission with EEN Vs CDED+PEN | week 14 |
| Measure | Description | Time Frame |
|---|---|---|
| ITT steroid free remission at week 8 | Induction of remission | week 8 |
| Microbiome composition difference between groups at week 14 | Assessment of microbiome composition and metabolomics |
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Inclusion criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rotem Sigall Boneh, RD | Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center | Principal Investigator |
| Michal Yaakov | Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr. Eytan Wine, | Edmonton | Canada | ||||
| Johan Van Limbergen |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24983973 | Background | Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease. Inflamm Bowel Dis. 2014 Aug;20(8):1353-60. doi: 10.1097/MIB.0000000000000110. | |
| 31170412 | Background |
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| Crohn's Disease Exclusion Diet | Other | a limited whole food diet |
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| Partial Enteral Nutrition | Other | 25-50% of Energy from formula |
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| Standard Exclusive Enteral Nutrition | Other | 8 weeks of Exclusive Enteral Nutrition |
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| week 14 |
| 3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment | Mucosal healing assessment | week 24 |
| Steroid and biologic free sustained remission at week 24. | Remission achieved and maintained without additional therapy | week 14 and 24 |
| Need for additional treatment to achieve remission by week 14 | Remission achieved without additional therapy | Week 14 |
| Mucosal healing as assessed by MRE in dietary responsive disease at week 52 | Mucosal healing | Week 52 |
| Halifax |
| Canada |
| Dr Sally Lawrence | Vancouver | Canada |
| Dr. Séamus Hussey | Dublin | Ireland |
| The E. Wolfson.Medical Center | Holon | 58100 | Israel |
| Dr. Francisco Javier Martin Carpi | Barcelona | Spain |
| Dr. Víctor Manuel Navas López | Málaga | Spain |
| 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. |
| 28525622 | Background | Sigall Boneh R, Sarbagili Shabat C, Yanai H, Chermesh I, Ben Avraham S, Boaz M, Levine A. Dietary Therapy With the Crohn's Disease Exclusion Diet is a Successful Strategy for Induction of Remission in Children and Adults Failing Biological Therapy. J Crohns Colitis. 2017 Oct 1;11(10):1205-1212. doi: 10.1093/ecco-jcc/jjx071. |
| 39732356 | Derived | Sigall Boneh R, Navas-Lopez VM, Hussey S, Pujol-Muncunill G, Lawrence S, Rolandsdotter H, Otley A, Martin-de-Carpi J, Abramas L, Herrador-Lopez M, Egea Castillo N, Chen M, Hurley M, Wingate K, Olen O, Eurenius Raaf T, Yaakov M, Wierdsma N, Van Limbergen J, Wine E. Modified Crohn's Disease Exclusion Diet Maintains Remission in Pediatric Crohn's Disease: Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2025 Oct;23(11):2001-2011. doi: 10.1016/j.cgh.2024.12.006. Epub 2024 Dec 26. |
| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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