Clinical trial NCT04777656: Use of Crohn's Disease Exclusion Diet on Top of Standard Therapy Versus Standard Therapy Alone in Unstable Pediatric Crohn's Disease Patients.
Official title: Randomized Trial for Unstable Pediatric Crohn's Disease Patients Comparing the Use of Crohn's Disease Exclusion Diet (CDED) on Top of Standard Therapy Versus Standard Therapy Alone.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's disease
Recurrent inflammatory disorder
Immunomodulators
Biologics
Exclusive Enteral Nutrition
Crohn's disease exclusion diet (CDED)
Modulen™IBD®
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: URC-CIC Paris Descartes Necker Cochin
name: MICALIS Institute
First posted: 2021-03-02
Enrollment: 120
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research is a multicenter French randomized and single blinded phase III clinical trial evaluating two treatment strategies among Crohn's disease (CD) patients. The main objective is to assess if the addition of Crohn's Disease Exclusion Diet (CDED) to ongoing standard medication is superior to reduce the rate of relapses over 12 months compared to standard medication alone in children/adolescents with unstable CD responding with remission after a 2-months course of CDED

Detailed description: Crohn's disease is a recurrent inflammatory disorder. Current treatment strategies aim reducing intestinal (and systemic) inflammation based on the use of Immunomodulators (IM) and biologics (B). However, some patients, particularly in the pediatric age group do not respond with remission to standard therapy and approximately 30% of patients lose response to efficient therapy. There is a clear unmet need for new treatment strategies. In addition, patients and families have a high degree of reluctance to use IM/B as life-long medication, particularly due to potential side effects including cancer, lymphomas, serious infections or drug-related immune diseases. This is of particular importance for children/adolescents with CD, potentially exposed over many decades to various IM/B. Experimental and epidemiological data indicate that the western life style and particularly modern food play a key role in the development of CD, probably via alteration of the intestinal barrier function and/or enforcing the intestinal dysbiosis. Based on these data and the observation that exclusive enteral nutrition is highly efficacious in inducing remission in active CD, nutritional therapies are more and more in the focus for the development of new treatment approaches.

The main objective is to assess if the addition of CDED to ongoing standard medication is superior to reduce the rate of relapses over 12 months compared to standard medication alone in children/adolescents with unstable CD responding with remission after a 2-months course of CDED.

To achieve this objective, eligible patients with active CD will participate to this study for a 13 months period. After a screening period, the patients will have a 2 months run-in phase where they will follow the CDED protocol, but continue their maintenance therapy, with the exception of corticosteroid that have to be tapered and stopped at the end of the 2 months.

Then, the patients responding to CDED during run-in will be randomized at M2 to one of the two treatment arms (CDED/Modulen™IBD® or Unrestricted food access) and will have 4 follow-up visits (M4, M6, M9 and M12)

Eligibility criteria: Inclusion Criteria:

* Child/Adolescent aged 6-17 years with a confirmed diagnosis of CD (for at least 3 months) with an active disease (defined as: wPCDAI \>12.5 or CRP \> 2 times upper limit or calprotectin levels \>250µg/g if available) despite anti-inflammatory (5-ASA and derivates), corticosteroids, immunomodulator (thiopurines or methotrexate) and/or biologic therapy (anti-TNF, anti-integrin anti-IL23 antibodies)
* For girls of childbearing age: a negative pregnancy test, and use of an effective method of contraception (abstinence, oral contraceptives, intra-uterine device, diaphragm with spermicide and condom)
* Patient willing to comply with daily intake of an exclusion diet
* Informed and signed consent of parents
* Patient affiliated to social security (or health insurance)

Exclusion Criteria:

* Active perianal fistulizing disease
* Internal fistula or evidence of un-drained and un-controlled abscess/phlegmon
* Patient who require CD-related surgical therapy
* Patient with known allergy to cow milk's proteins
* Patient incapable to follow CDED for a prolonged period
* Pregnancy, breastfeeding
* Patient already included in an interventional study

Primary outcomes:
measure: Relapse from randomization until M12
timeFrame: 12 months
Secondary outcomes:
measure: Change of wPCDAI from baseline to M2
timeFrame: 2 months
measure: Change of fecal calprotectin values from baseline to M2
timeFrame: 2 months
measure: Clinical remission at M2
timeFrame: 2 months
measure: Deep remission at M2
timeFrame: 2 months
measure: Physician global assessment (PGA) from baseline to M2
timeFrame: 2 months
measure: Mucosal healing at M2
timeFrame: 2 months
measure: Endoscopic response at M2
timeFrame: 2 months
measure: Change of MRI from baseline to M2
timeFrame: 2 months
measure: CDED tolerance rate at M2
timeFrame: 2 months
measure: CDED compliance rate at M2
timeFrame: 2 months
measure: Change of intestinal microbiome composition from baseline to M2
timeFrame: 2 months
measure: Clinical remission
timeFrame: At 4 months, 6 months, 9 months and 12 months
measure: Deep remission
timeFrame: At 4 months, 6 months, 9 months and 12 months
measure: Relapse
timeFrame: At 4 months, 6 months, 9 months and 12 months
measure: Physician global assessment (PGA)
timeFrame: At 4 months, 6 months, 9 months and 12 months
measure: Mucosal Healing at M12
timeFrame: 12 months
measure: Endoscopic response at M12
timeFrame: 12 months
measure: Change of MRI from M2 to M12
timeFrame: 12 months
measure: CDED tolerance rate at M12
timeFrame: 12 months
measure: CDED compliance rate at M12
timeFrame: 12 months
measure: Change of Intestinal microbiome composition
timeFrame: At 4 months, 6 months, 9 months, 12 months
measure: Change of quality of life IMPACT-3 from inclusion until 12 months
timeFrame: At baseline, 2 months, 4 months, 6 months, 9 months, 12 months
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Femme mère enfant, CHU Lyon - Service Hépato-gastroentérologie et Nutrition pédiatrique
city: Caen
country: France
facility: CHU Caen Normandie - Service de Gastroentérologie pédiatrique
city: Marseille
country: France
facility: Hôpital de la Timone, AP-HM - Service de Gastroentérologie pédiatrique
city: Paris
country: France
facility: Hôpital Necker-Enfants malades - Service de Gastroentérologie pédiatrique
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Franck Ruemmele, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Wynands J, Belbouab R, Candon S, Talbotec C, Mougenot JF, Chatenoud L, Schmitz J, Cezard JP, Goulet O, Hugot JP, Ruemmele FM. 12-month follow-up after successful infliximab therapy in pediatric crohn disease. J Pediatr Gastroenterol Nutr. 2008 Mar;46(3):293-8. doi: 10.1097/MPG.0b013e31815604cd.
citation: Pigneur B, Lepage P, Mondot S, Schmitz J, Goulet O, Dore J, Ruemmele FM. Mucosal Healing and Bacterial Composition in Response to Enteral Nutrition Vs Steroid-based Induction Therapy-A Randomised Prospective Clinical Trial in Children With Crohn's Disease. J Crohns Colitis. 2019 Jul 25;13(7):846-855. doi: 10.1093/ecco-jcc/jjy207.
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: Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018 Sep;67(9):1726-1738. doi: 10.1136/gutjnl-2017-315866. Epub 2018 May 18.