Comparison of Partial and Exclusive Enteral Nutrition in the Treatment of Active Childhood-onset Crohn's Disease

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.

Study Overview

• Status: Unknown
• Conditions: Adolescent; Child; Crohn Disease; Enteral Nutrition; Diet; Remission
• Intervention / Treatment: Other: ALICALM (75% of daily caloric requirements); Other: ALICALM (100% of daily caloric requirements)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • University Medical Centre Ljubljana
    • Contact: Darja Urlep, MD, MSc; Phone Number: 0038631646347; Email: darja.urlep@gmail.com
    • Contact: Evgen Benedik, PhD; Phone Number: 0038631745549; Email: evgen.benedik@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: PEN group; Partial enteral nutrition (PEN) group will receive 75% of their daily dietary needs from a polymeric formula (Alicalm, Nutricia) and a limited (25% of dietary needs = 1 meal per day) from an antiinflammatory diet for CD (AID-CD) for 6 weeks.	Other: ALICALM (75% of daily caloric requirements); PEN group will receive 75% of their daily dietary needs from a polymeric formula (Alicalm, Nutricia) and 25% of daily dietary needs (1 meal per day) from an antiinflammatory diet for CD (AID-CD) for 6 weeks.
Active Comparator: EEN group; Exclusive enteral nutrition (EEN) group will receive 100 % of their daily caloric requirements from a poymeric formula (Alicalm, Nutricia) for 6 weeks.	Other: ALICALM (100% of daily caloric requirements); EEN group will receive 100% of their daily dietary needs from a polymeric formula (Alicalm, Nutricia) for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission	Clinical Remission (Pediatric Crohn's Disease Activity Index <10) on an intention to treat principle after 6 weeks of therapy.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	- Clinical response defined as a decrease in Pediatric Crohn's Disease Activity Index score of ≥12.5 points) for children or a drop in HBI of at least 2 points in young adults	6 weeks
Mucosal healing	Mucosal healing using the Simple Endoscopic Score for CD (SES-CD)	6-8 weeks
Change in SES-CD	Change in SES-CD from baseline to 6 weeks	At week 0 and 6 -8 weeks following enrollment
Changes in specific blood tests	Changes in specific blood tests such as erythrocyte sedimentation rate (ESR), C reactive protein, hemoglobin, albumin, and platelets from baseline to 6 weeks	At the 1, 3 and 6 weeks visits
Changes in stool calprotectin concentrations	Changes in stool calprotectin concentrations (mg/kg) from baseline to 6 weeks	At the 3 and 6 weeks visits
Changes in weight-z-scores	Changes in weight-z-scores	At the 0 and 6 weeks visits
Changes in ITM -z-scores	Changes in ITM -z-scores	At the 0 and 6 weeks visits

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Investigators: Study Chair: Rok Orel, MD, PhD, University Medical Centre Ljubljana, University Children's Hospital Ljubljana, Department of gastroenterology, hepatology and nutrition

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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Anticipated): July 31, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: May 25, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 20150146

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