Use of Crohn's Disease Exclusion Diet on Top of Standard Therapy Versus Standard Therapy Alone in Unstable Pediatric Crohn's Disease Patients.

Phase 3RecruitingNCT04777656

Assistance Publique - Hôpitaux de Paris120 enrolled

Overview

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

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)

Study Type

INTERVENTIONAL

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (4)

Hôpital Femme mère enfant, CHU Lyon - Service Hépato-gastroentérologie et Nutrition pédiatrique

Bron, France

RECRUITING

CHU Caen Normandie - Service de Gastroentérologie pédiatrique

Caen, France

RECRUITING

Hôpital de la Timone, AP-HM - Service de Gastroentérologie pédiatrique

Marseille, France

RECRUITING

Hôpital Necker-Enfants malades - Service de Gastroentérologie pédiatrique

Paris, France

RECRUITING

Outcomes

Primary Outcomes

Relapse from randomization until M12

Relapse is defined as weighted Paediatric Crohn's disease activity index (wPCDAI) \>40 points and/or CRP \>2 times over upper limit (in the absence of any obvious infections sign) or if at two consecutive visits (within 2-8 weeks) the wPCDAI is \>12,5 but less 40 and/or CRP \>1,5 but less 2 times over upper limit (in the absence of any obvious infections sign) or if the patient required additional CD-specific medication/surgery in the interval.

Time frame: 12 months

Secondary Outcomes

Change of wPCDAI from baseline to M2

Time frame: 2 months

Change of fecal calprotectin values from baseline to M2

Time frame: 2 months

Clinical remission at M2

Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)

Time frame: 2 months

Deep remission at M2

Defined as wPCDAI ≤12.5 and normal CRP within normal lab range) and normal fecal calprotectin ((\<250µg/g)

Time frame: 2 months

Physician global assessment (PGA) from baseline to M2

Crohn's Disease activity assessed as remission - weak - moderate - severe

Time frame: 2 months

Mucosal healing at M2

absence of any ulcerations (including aphthae)

Time frame: 2 months

Endoscopic response at M2

Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline

Time frame: 2 months

Change of MRI from baseline to M2

Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from baseline to M2

Time frame: 2 months

CDED tolerance rate at M2

serious and non serious adverse events

Time frame: 2 months

CDED compliance rate at M2

Time frame: 2 months

Change of intestinal microbiome composition from baseline to M2

Time frame: 2 months

Clinical remission

Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)

Time frame: At 4 months, 6 months, 9 months and 12 months

Deep remission

Defined as wPCDAI ≤12.5 and normal CRP (within normal lab range) and normal fecal calprotectin (\<250µg/g)

Time frame: At 4 months, 6 months, 9 months and 12 months

Relapse

Defined as wPCDAI \>40 points and/or CRP \>2 times over upper limit (in the absence of any obvious infections sign) or if at two consecutive visits (within 2-8 weeks) the wPCDAI is \>12,5 but less 40 and/or CRP \>1,5 but less 2 times over upper limit (in the absence of any obvious infections sign) or if the patient required additional CD-specific medication/surgery in the interval

Time frame: At 4 months, 6 months, 9 months and 12 months

Physician global assessment (PGA)

Crohn's Disease activity assessed as remission - weak - moderate - severe

Time frame: At 4 months, 6 months, 9 months and 12 months

Mucosal Healing at M12

Absence of any ulcerations (including aphthae)

Time frame: 12 months

Endoscopic response at M12

Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline

Time frame: 12 months

Change of MRI from M2 to M12

Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from M2 to M12

Time frame: 12 months

CDED tolerance rate at M12

Serious and non serious adverse events

Time frame: 12 months

CDED compliance rate at M12

Time frame: 12 months

Change of Intestinal microbiome composition

Time frame: At 4 months, 6 months, 9 months, 12 months

Change of quality of life IMPACT-3 from inclusion until 12 months

IMPACT-3 questionnaire of 35 closed questions - scale ranging from 1 to 5 for all answers - higher score suggesting better quality of life

Time frame: At baseline, 2 months, 4 months, 6 months, 9 months, 12 months

Use of Crohn's Disease Exclusion Diet on Top of Standard Therapy Versus Standard Therapy Alone in Unstable Pediatric Crohn's Disease Patients.

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts