Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease

NCT ID: NCT02843100

Last Updated: 2022-06-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-10

Study Completion Date

2022-05-29

Brief Summary

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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

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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.

Conditions

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Crohn's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Modified Exclusive Enteral Nutrition

Intervention Type OTHER

Two weeks of Exclusive Enteral Nutrition with Modulen

Crohn's Disease Exclusion Diet

Intervention Type OTHER

a limited whole food diet

Partial Enteral Nutrition

Intervention Type OTHER

25-50% of Energy from formula

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.

Group Type ACTIVE_COMPARATOR

Partial Enteral Nutrition

Intervention Type OTHER

25-50% of Energy from formula

Standard Exclusive Enteral Nutrition

Intervention Type OTHER

8 weeks of Exclusive Enteral Nutrition

Interventions

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Modified Exclusive Enteral Nutrition

Two weeks of Exclusive Enteral Nutrition with Modulen

Intervention Type OTHER

Crohn's Disease Exclusion Diet

a limited whole food diet

Intervention Type OTHER

Partial Enteral Nutrition

25-50% of Energy from formula

Intervention Type OTHER

Standard Exclusive Enteral Nutrition

8 weeks of Exclusive Enteral Nutrition

Intervention Type OTHER

Other Intervention Names

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Modulen, Nestle CDED Modulen, Nestle Modulen, Nestle

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prof. Arie Levine

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof. Arie Levine

Director, Pediatric Gastroenterology and Nutrition unit

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rotem Sigall Boneh, RD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center

Michal Yaakov

Role: STUDY_DIRECTOR

Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center

Locations

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Dr. Eytan Wine,

Edmonton, , Canada

Site Status

Johan Van Limbergen

Halifax, , Canada

Site Status

Dr Sally Lawrence

Vancouver, , Canada

Site Status

Dr. Séamus Hussey

Dublin, , Ireland

Site Status

The E. Wolfson.Medical Center

Holon, , Israel

Site Status

Dr. Francisco Javier Martin Carpi

Barcelona, , Spain

Site Status

Dr. Víctor Manuel Navas López

Málaga, , Spain

Site Status

Countries

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Canada Ireland Israel Spain

References

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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.

Reference Type BACKGROUND
PMID: 24983973 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31170412 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28525622 (View on PubMed)

Sigall Boneh R, Navas-Lopez VM, Hussey S, Pujol-Muncunill G, Lawrence S, Rolandsdotter H, Otley A, Martin-de-Carpi J, Abramas L, Herrador-Lopez M, Egea Castillo N, Chen M, Hurley M, Wingate K, Olen O, Eurenius Raaf T, Yaakov M, Wierdsma N, Van Limbergen J, Wine E. Modified Crohn's Disease Exclusion Diet Maintains Remission in Pediatric Crohn's Disease: Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2025 Oct;23(11):2001-2011. doi: 10.1016/j.cgh.2024.12.006. Epub 2024 Dec 26.

Reference Type DERIVED
PMID: 39732356 (View on PubMed)

Other Identifiers

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0075-16 WOMC

Identifier Type: -

Identifier Source: org_study_id

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