Use of Crohn's Disease Exclusion Diet on Top of Standard Therapy Versus Standard Therapy Alone in Unstable Pediatric Crohn's Disease Patients.
- Conditions
- Crohn's Disease
- Registration Number
- NCT04777656
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Relapse from randomization until M12 12 months 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.
- Secondary Outcome Measures
Name Time Method Change of fecal calprotectin values from baseline to M2 2 months Physician global assessment (PGA) from baseline to M2 2 months Crohn's Disease activity assessed as remission - weak - moderate - severe
Mucosal healing at M2 2 months absence of any ulcerations (including aphthae)
Clinical remission At 4 months, 6 months, 9 months and 12 months Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)
Relapse At 4 months, 6 months, 9 months and 12 months 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
Mucosal Healing at M12 12 months Absence of any ulcerations (including aphthae)
CDED compliance rate at M12 12 months Change of wPCDAI from baseline to M2 2 months CDED compliance rate at M2 2 months Change of quality of life IMPACT-3 from inclusion until 12 months At baseline, 2 months, 4 months, 6 months, 9 months, 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
CDED tolerance rate at M2 2 months serious and non serious adverse events
Physician global assessment (PGA) At 4 months, 6 months, 9 months and 12 months Crohn's Disease activity assessed as remission - weak - moderate - severe
Clinical remission at M2 2 months Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)
Deep remission at M2 2 months Defined as wPCDAI ≤12.5 and normal CRP within normal lab range) and normal fecal calprotectin ((\<250µg/g)
Endoscopic response at M2 2 months Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline
Change of MRI from baseline to M2 2 months Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from baseline to M2
Change of intestinal microbiome composition from baseline to M2 2 months Endoscopic response at M12 12 months Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline
Change of MRI from M2 to M12 12 months Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from M2 to M12
CDED tolerance rate at M12 12 months Serious and non serious adverse events
Deep remission At 4 months, 6 months, 9 months and 12 months Defined as wPCDAI ≤12.5 and normal CRP (within normal lab range) and normal fecal calprotectin (\<250µg/g)
Change of Intestinal microbiome composition At 4 months, 6 months, 9 months, 12 months
Trial Locations
- Locations (4)
CHU Caen Normandie - Service de Gastroentérologie pédiatrique
🇫🇷Caen, France
Hôpital de la Timone, AP-HM - Service de Gastroentérologie pédiatrique
🇫🇷Marseille, France
Hôpital Necker-Enfants malades - Service de Gastroentérologie pédiatrique
🇫🇷Paris, France
Hôpital Femme mère enfant, CHU Lyon - Service Hépato-gastroentérologie et Nutrition pédiatrique
🇫🇷Bron, France