Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease (DIETOMICS-CD)

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Other: Modified Exclusive Enteral Nutrition; Other: Crohn's Disease Exclusion Diet; Other: Partial Enteral Nutrition; Other: Standard Exclusive Enteral Nutrition

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 Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Edmonton, Canada
    • Dr. Eytan Wine,
  • Halifax, Canada
    • Johan Van Limbergen
  • Vancouver, Canada
    • Dr Sally Lawrence
• Ireland
  • Dublin, Ireland
    • Dr. Séamus Hussey
• Israel
  • Holon, Israel, 58100
    • The E. Wolfson.Medical Center
• Spain
  • Barcelona, Spain
    • Dr. Francisco Javier Martin Carpi
  • Málaga, Spain
    • Dr. Víctor Manuel Navas López

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Prof. Arie Levine
• Investigators: Principal Investigator: Rotem Sigall Boneh, RD, Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center; Study Director: Michal Yaakov, Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Actual): May 29, 2022
• Study Completion (Actual): May 29, 2022

Study Registration Dates

• First Submitted: June 22, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 29, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Microbiome; Pediatric; Diet; Crohn's Disease; Exclusive Enteral Nutrition
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 0075-16 WOMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No