Clinical trial NCT03176875: Comparison of Partial and Exclusive Enteral Nutrition in the Treatment of Active Childhood-onset Crohn's Disease
Official title: Comparison of Partial and Exclusive Enteral Nutrition in the Treatment of Active Childhood-onset Crohn's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adolescent
Child
Diet
Crohn Disease
Enteral Nutrition
Remission
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2017-06-06
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the efficacy of a novel enteral nutrition (EN) protocol (delivering 75% of patient's caloric needs through EN) for induction of remission in patients with active childhood-onset Crohn's disease (CD) and compare it to the standard protocol with exclusive enteral nutrition (EEN). This novel approach allows patients to consume remaining calories (25%) from an antiinflammatory diet for CD (AID-CD).

The hypothesis is that no significant difference in the remission rate between the novel EN protocol with partial enteral nutrition (PEN) and standard protocol with EEN will be observed.

Detailed description: Background: Exclusive enteral nutrition (EEN) is a well established method of treatment for inducing remission in childhood-onset Crohn's disease. It involves placing children on a strict diet composed only of a single polymeric formula, as the sole source of nutrition over 6 to 8 weeks. Use of this treatment method results in clinical remission in 50% to 80% of children by week 6-8.

Partial enteral nutrition (PEN) would be more acceptable to patients than EEN, and might be an effective treatment for active Crohn's disease. Moreover, there are studies suggesting that PEN may be effective for the induction of remission in pediatric patients with Crohn's disease; however, the level of evidence is still low.

Methods: This is a prospective randomized controlled trial, in patients with active childhood-onset Crohn's disease comparing two arms over 6 weeks of therapy.

Group 1 (PEN group): will receive 75% of their dietary needs from a polymeric formula (Alicalm, Nutricia) and a limited (25% of dietary needs = 1 meal per day) whole food AID-CD for 6 weeks.

Group 2 (EEN group): will receive EEN with Alicalm (Nutricia) for 6 weeks.

Patients will be seen at onset and week 1, 3, and 6.

This study will evaluate clinical response (a decrease in PCDAI score of ≥12.5 points), clinical remission (PCDAI \<10) and mucosal healing using SES-CD in both groups, as well as the effects of the two nutritional approaches on the patients' nutritional status.

Antiinflammatory diet for Crohn's disease (AID-CD) is based on reducing exposure to animal fat, simple carbohydrates and processed food. We removed foods that previous research has shown to induce inflammation and added foods that have been shown to be beneficial in reducing inflammation. Our AID-CD is based on Central European and thus Slovenian local and traditional cuisine.

Eligibility criteria: Inclusion Criteria:

* Children (4 - 18 years of age)
* Young adults (\>18 and ≤ 30 years of age) with childhood-onset CD (the diagnosis of CD before 18 years of age)
* Assured diagnosis of Crohn's disease according to the Porto criteria
* Patients with Active CD (Pediatric Crohn's Disease Activity Index (PCDAI) ≥10 in children or Harvey-Bradshaw Index (HBI) \>3 in young adults )
* Patients with new-onset CD and patients with active disease despite stable doses of concomitant therapy with immunomodulators (thiopurines, methotrexate, tacrolimus) for ≥ 3 months, on stable doses of biologic therapy (anti-TNF-a agents) for ≥ 2 months
* Patients will not be excluded if they start therapy with thiopurine concurrently, as thiopurines are not considered sufficient to induce remission in active disease before 8 weeks
* Written consent of the patient and/or the legal guardian

Exclusion Criteria:

* Patients with no disease activity ( PCDAI \<10)
* Patients who have received corticosteroids of any kind in the previous 4 weeks.
* Patients with penetrating disease (abscess or fistula)
* Active Perianal disease
* Active Extraintestinal disease
* Sclerosing Cholangitis
* Patients with fixed stricture or small bowel obstruction
* If the patients had received any other medication for inducing remission such as steroids and/or antibiotics
* No consent of the patient and/or the legal guardian

Primary outcomes:
measure: Clinical Remission
timeFrame: 6 weeks
Secondary outcomes:
measure: Clinical response
timeFrame: 6 weeks
measure: Mucosal healing
timeFrame: 6-8 weeks
measure: Change in SES-CD
timeFrame: At week 0 and 6 -8 weeks following enrollment
measure: Changes in specific blood tests
timeFrame: At the 1, 3 and 6 weeks visits
measure: Changes in stool calprotectin concentrations
timeFrame: At the 3 and 6 weeks visits
measure: Changes in weight-z-scores
timeFrame: At the 0 and 6 weeks visits
measure: Changes in ITM -z-scores
timeFrame: At the 0 and 6 weeks visits
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: University Medical Centre Ljubljana, University Children's Hospital Ljubljana, Department of gastroenterology, hepatology and nutrition
name: Rok Orel, MD, PhD
role: STUDY_CHAIR
References:
citation: Gupta K, Noble A, Kachelries KE, Albenberg L, Kelsen JR, Grossman AB, Baldassano RN. A novel enteral nutrition protocol for the treatment of pediatric Crohn's disease. Inflamm Bowel Dis. 2013 Jun;19(7):1374-8. doi: 10.1097/MIB.0b013e318281321b.
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: Urlep D, Benedik E, Brecelj J, Orel R. Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn's disease: results of a prospective cohort study. Eur J Pediatr. 2020 Mar;179(3):431-438. doi: 10.1007/s00431-019-03520-7. Epub 2019 Nov 28.