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

Prof. Arie Levine63 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Crohn's Disease

Interventions

Modified Exclusive Enteral NutritionOTHER

Two weeks of Exclusive Enteral Nutrition with Modulen

Crohn's Disease Exclusion DietOTHER

a limited whole food diet

Partial Enteral NutritionOTHER

25-50% of Energy from formula

Eligibility

Sex: ALLMin age: 8 YearsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Established diagnosis of Crohn's disease. 2. Patients with mild to severe active Crohn's disease (15≤PCDAI≤47.5) 3. Ages 8-18 4. Duration of disease ≤ 36 months 5. Active inflammation (CRP≥\>0.6 mg /dL or ESR≥\>20 or Calprotectin≥\>200 mcg/gr within the past 3 weeks) during screening 6. Patients with B1, P0 uncomplicated disease at enrollment 7. 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) 8. Signed informed consent Exclusion Criteria: 1. Patients with very mild disease (PCDAI 12.5 -15) or very severe disease (PCDAI \>47.5) 2. Pregnancy 3. Patients who have disease confined to the colon involving the descending colon, rectum or sigmoid colon and no prior history of small bowel involvement 4. Patients who have active extra intestinal disease (such as Arthritis, Uveitis, Pyoderma Gangrenosum, Erythema Nodosum etc.) 5. Patients with complicated disease (B2, B3) 6. Patients who recently onset use of an immunomodulator \<8 weeks, or dose change in past 8 weeks. 7. Patients with current use of biologics, or use in last 8 weeks or current use of systemic steroids 8. Patients who have active perianal disease ( active fistula or abscess) 9. 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. 10. Patients with fever \> 38.3 11. Documented milk protein allergy

Locations (7)

Dr. Eytan Wine,

Edmonton, Canada

Johan Van Limbergen

Halifax, Canada

Dr Sally Lawrence

Vancouver, Canada

Dr. Séamus Hussey

Dublin, Ireland

Outcomes

Primary Outcomes

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

Time frame: week 14

Secondary Outcomes

ITT steroid free remission at week 8

Induction of remission

Time frame: week 8

Microbiome composition difference between groups at week 14

Assessment of microbiome composition and metabolomics

Time frame: week 14

3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment

Mucosal healing assessment

Time frame: week 24

Steroid and biologic free sustained remission at week 24.

Remission achieved and maintained without additional therapy

Time frame: week 14 and 24

Need for additional treatment to achieve remission by week 14

Remission achieved without additional therapy

Time frame: Week 14

Mucosal healing as assessed by MRE in dietary responsive disease at week 52

Mucosal healing

Time frame: Week 52

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.