Clinical trial NCT01728870: Partial Enteral Nutrition With a Unique Diet vs. Exclusive Enteral Nutrition for the Treatment of Pediatric Crohn's Disease
Official title: Comparison of Partial Enteral Nutririon (Modulen) With a Unique Diet to Exclusive Enteral Nutrition (Modulen) for the Treatment of Pediatric Crohn's Disease. A Prospective Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Keywords: Pediatric
Crohn's disease
Mild to moderate Crohn's Disease
Diet
Enteral Nutrition
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2012-11-20
Enrollment: 74
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and tolerability of a novel dietary intervention for early CD based on partial enteral nutrition, and to compare it to the gold standard but difficult to implement dietary intervention- Exclusive enteral nutrition with Modulen .

Detailed description: Background: Crohn's disease is clearly on the rise in countries exposed to industrialization and western diet. Several factors may implicate diet in the pathogenesis of CD or in disease activity. The strongest argument for an effect of diet is the effect of exclusive enteral nutrition (EEN) on disease activity in CD. 40-80% of children , fed an exclusive liquid diet, irrespective of which diet, will enter complete remission, often with normalization of inflammatory markers. The effect of formula has been shown to be independent of fat or protein composition in pediatric studies, but to be dependent on exclusion of normal diet.Thus, rather than the composition of EEN being associated with remission of disease it may be the exclusion of certain components of the Western diet may be responsible for improvement.

Methods:This is a prospective randomized controlled trial, in patients with a recent diagnosis of CD (up to two years),aged 4-18, comparing two arms over 12 weeks of therapy.

Group 1:will receive 50% of their dietary needs from a polymeric formula ( Modulen, Nestle) and a limited whole food diet for 6 weeks/ Group 2: will receive EEN with Modulen for 6 weeks. At the end of 6 weeks, all patients entering remission (irrespective of randomization) will enter the second 6 week phase, continuing 25 % of calories as Modulen in both groups. Patients in remission from group 2 will continue to consume 25% of calories as Modulen and be allowed free diet , patients in Group 1 will continue 25% of calories from Modulen but continue restricted diet.

Patients will be seen at onset (week 0), weeks 3 and 6, 12 and 24 weeks.

We hypothesize that by withdrawing the offending dietary agents we can achieve an equal remission rate with improved tolerability. This study will evaluate response, remission and tolerability in both groups, as well as the effects of nutrition on bone health.

Eligibility criteria: Inclusion Criteria:

1. Children 4-18 years of age.
2. Patients with a diagnosis of CD-duration of disease up to 36 months
3. Have macroscopic small bowel involvement, or isolated large bowel disease confined to the right or transverse colon
4. Patients with a pediatric activity index -PCDAI ≥ 10
5. Patients will not be excluded if they have received 5ASA or an immunomodulator for \>8 weeks and the dose is stable , or if they start a thiopurine concurrently , as thiopurines are not considered sufficient to induce remission in active disease before 8 weeks as an isolated therapy.
6. Informed Consent

Exclusion Criteria:

1. Patients with no disease activity ( PCDAI \<10) or severe disease ( PCDAI ≥ 40).
2. Patients who have received corticosteroids of any kind in the previous 4 weeks.
3. Patients who have started an immunomodulator in the previous 8 weeks
4. Any current biological treatment
5. Isolated Large bowel disease ( L2) involving the recto-sigmoid or descending colon
6. Patients with penetrating disease (abscess or fistula)
7. Active Perianal disease
8. Fixed stricture or small bowel obstruction
9. Normal CRP and ESR
10. Active joint disease.
11. Patients who have undergone an intestinal resection.
12. Sclerosing Cholangitis
13. Pregnancy

Primary outcomes:
measure: patient's adherence with the diet assessed by cessation of therapy because of patients refusal to continue and by a MARS questionnaire
timeFrame: 6 weeks
Secondary outcomes:
measure: Response, defined as a drop in PCDAI of 12.5 points or remission, on an intention to treat analysis.
timeFrame: 6 weeks
measure: Remission at week 6 and week 12 (defined as PCDAI≤10, or less than 7.5 without height component),
timeFrame: 6 weeks and 12 weeks
measure: Bone health
timeFrame: at the 3, and 6 month visits
measure: CRP at week 12
timeFrame: 12 weeks
measure: Physician assessment of compliance
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Holon
country: Israel
facility: The E. Wolfson.Medical Center
Study officials:
affiliation: Pediatric Gastroenterology and Nutrition unit, Wolfson MC
name: Arie Levine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Verburgt CM, Dunn KA, Ghiboub M, Lewis JD, Wine E, Sigall Boneh R, Gerasimidis K, Shamir R, Penny S, Pinto DM, Cohen A, Bjorndahl P, Svolos V, Bielawski JP, Benninga MA, de Jonge WJ, Van Limbergen JE. Successful Dietary Therapy in Paediatric Crohn's Disease is Associated with Shifts in Bacterial Dysbiosis and Inflammatory Metabotype Towards Healthy Controls. J Crohns Colitis. 2023 Jan 27;17(1):61-72. doi: 10.1093/ecco-jcc/jjac105.
citation: Ghiboub M, Penny S, Verburgt CM, Boneh RS, Wine E, Cohen A, Dunn KA, Pinto DM, Benninga MA, de Jonge WJ, Levine A, Van Limbergen JE. Metabolome Changes With Diet-Induced Remission in Pediatric Crohn's Disease. Gastroenterology. 2022 Oct;163(4):922-936.e15. doi: 10.1053/j.gastro.2022.05.050. Epub 2022 Jun 7.
citation: Sigall Boneh R, Van Limbergen J, Wine E, Assa A, Shaoul R, Milman P, Cohen S, Kori M, Peleg S, On A, Shamaly H, Abramas L, Levine A. Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn's Disease. Clin Gastroenterol Hepatol. 2021 Apr;19(4):752-759. doi: 10.1016/j.cgh.2020.04.006. Epub 2020 Apr 14.
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.