Clinical trial NCT02843100: Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease
Official title: Modified Exclusive Enteral Nutrition With the Crohn's Disease Exclusion Diet for Induction and Maintenance of Remission and Re-biosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Pediatric
Exclusive Enteral Nutrition
Diet
Microbiome
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2016-07-25
Enrollment: 63
Sex: ALL
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: ITT, steroid free Clinical remission (defined as Pediatric Crohn's Disease Activity Index (PCDAI)<10) at week 14
timeFrame: week 14
Secondary outcomes:
measure: ITT steroid free remission at week 8
timeFrame: week 8
measure: Microbiome composition difference between groups at week 14
timeFrame: week 14
measure: 3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment
timeFrame: week 24
measure: Steroid and biologic free sustained remission at week 24.
timeFrame: week 14 and 24
measure: Need for additional treatment to achieve remission by week 14
timeFrame: Week 14
measure: Mucosal healing as assessed by MRE in dietary responsive disease at week 52
timeFrame: Week 52
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Dr. Eytan Wine,
city: Halifax
country: Canada
facility: Johan Van Limbergen
city: Vancouver
country: Canada
facility: Dr Sally Lawrence
city: Dublin
country: Ireland
facility: Dr. Séamus Hussey
city: Holon
country: Israel
facility: The E. Wolfson.Medical Center
city: Barcelona
country: Spain
facility: Dr. Francisco Javier Martin Carpi
city: Málaga
country: Spain
facility: Dr. Víctor Manuel Navas López
Study officials:
affiliation: Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center
name: Rotem Sigall Boneh, RD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center
name: Michal Yaakov
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.