Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Modified Exclusive Enteral Nutrition With the Crohn's Disease Exclusion Diet for Induction and Maintenance of Remission and Re-biosis

Conditions
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Crohn's Disease

Intervention / Treatment
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* Other: Modified Exclusive Enteral Nutrition
* Other: Crohn's Disease Exclusion Diet
* Other: Partial Enteral Nutrition
* Other: Standard Exclusive Enteral Nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Established diagnosis of Crohn's disease. Patients with mild to severe active Crohn's disease (15≤PCDAI≤47.5) Ages 8-18 Duration of disease ≤ 36 months Active inflammation (CRP≥>0.6 mg /dL or ESR≥>20 or Calprotectin≥>200 mcg/gr within the past 3 weeks) during screening Patients with B1, P0 uncomplicated disease at enrollment Patients with disease defined as L1, L4, L3 or L2 limited to cecum, ascending or transverse colon or L2 with left sided disease with terminal ileum or small bowel involvement in the past by the Paris classification (patients with macroscopic disease) Signed informed consent Exclusion Criteria: Patients with very mild disease (PCDAI 12.5 -15) or very severe disease (PCDAI >47.5) Pregnancy Patients who have disease confined to the colon involving the descending colon, rectum or sigmoid colon and no prior history of small bowel involvement Patients who have active extra intestinal disease (such as Arthritis, Uveitis, Pyoderma Gangrenosum, Erythema Nodosum etc.) Patients with complicated disease (B2, B3) Patients who recently onset use of an immunomodulator <8 weeks, or dose change in past 8 weeks. Patients with current use of biologics, or use in last 8 weeks or current use of systemic steroids Patients who have active perianal disease ( active fistula or abscess) Patients who have positive stool cultures with relevant pathogens,, or positive tests for parasites or C. difficile. Stool tests are mandatory only if diarrhea is present. Patients with fever > 38.3 Documented milk protein allergy

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>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 | Other: Modified Exclusive Enteral Nutrition<br>* Two weeks of Exclusive Enteral Nutrition with Modulen<br>* Other names: Modulen, Nestle;Other: Crohn's Disease Exclusion Diet<br>* a limited whole food diet<br>* Other names: CDED;Other: Partial Enteral Nutrition<br>* 25-50% of Energy from formula<br>* Other names: Modulen, Nestle;|
| Active Comparator: Group 2<br>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. | Other: Partial Enteral Nutrition<br>* 25-50% of Energy from formula<br>* Other names: Modulen, Nestle;Other: Standard Exclusive Enteral Nutrition<br>* 8 weeks of Exclusive Enteral Nutrition<br>* Other names: Modulen, Nestle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Pediatric, Exclusive Enteral Nutrition, Diet, Microbiome