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

Not Applicable

Completed

• Conditions: Crohn's Disease
• Interventions: Other: Partial Enteral Nutrition; Other: Modified Exclusive Enteral Nutrition; Other: Crohn's Disease Exclusion Diet; Other: Standard Exclusive Enteral Nutrition

• Registration Number: NCT02843100
• Lead Sponsor: Prof. Arie Levine

Brief Summary

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

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 Timeline

• Study First Submitted: 2016-06-22
• Study First Submitted QC: 2016-07-20
• Study First Posted: 2016-07-25
• Study Start: 2018-04-10
• Status Verified: 2022-05
• Primary Completion: 2022-05-29
• Study Completion: 2022-05-29
• Last Update Submitted: 2022-05-29
• Last Update Posted: 2022-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Crohn's Disease Exclusion Diet	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
Group 2	Standard Exclusive Enteral Nutrition	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.
Group 2	Partial Enteral Nutrition	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.
Group 1	Partial Enteral Nutrition	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
Group 1	Modified Exclusive Enteral Nutrition	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

Primary Outcome Measures

Name	Time	Method
ITT, steroid free Clinical remission (defined as Pediatric Crohn's Disease Activity Index (PCDAI)<10) at week 14	week 14	Sustained remission with EEN Vs CDED+PEN

Secondary Outcome Measures

Name	Time	Method
Microbiome composition difference between groups at week 14	week 14	Assessment of microbiome composition and metabolomics
Steroid and biologic free sustained remission at week 24.	week 14 and 24	Remission achieved and maintained without additional therapy
Need for additional treatment to achieve remission by week 14	Week 14	Remission achieved without additional therapy
Mucosal healing as assessed by MRE in dietary responsive disease at week 52	Week 52	Mucosal healing
ITT steroid free remission at week 8	week 8	Induction of remission
3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment	week 24	Mucosal healing assessment

Trial Locations

Locations (7)

Dr. Francisco Javier Martin Carpi; 🇪🇸 Barcelona, Spain

Dr Sally Lawrence; 🇨🇦 Vancouver, Canada

Dr. Eytan Wine,; 🇨🇦 Edmonton, Canada

Johan Van Limbergen; 🇨🇦 Halifax, Canada

Dr. Víctor Manuel Navas López; 🇪🇸 Málaga, Spain

The E. Wolfson.Medical Center; 🇮🇱 Holon, Israel

Dr. Séamus Hussey; 🇮🇪 Dublin, Ireland