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Cyclic Exclusive Enteral Nutrition as Maintenance Therapy for Pediatric Crohn's Disease

Not Applicable
Completed
Conditions
Crohn's Disease
Interventions
Dietary Supplement: MODULEN IBD
Registration Number
NCT02201693
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

The purpose of this study is to compare the rate of first relapse at 12 months between maintenance therapy with cyclic exclusive enteral nutrition (EEN) (at least 100% daily calories) and maintenance therapy with supplementary enteral nutritional support (25% daily calories).

Detailed Description

Enteral nutrition (EN) is a highly efficacious treatment option for Crohn's disease (CD). In children, exclusive EN is considered first choice therapy to induce remission in pediatric CD, as highlighted in the recent ESPGHAN-ECCO guidelines. Several meta-analyses showed that the anti-inflammatory potential of EEN is comparable to the effects of steroids. In addition, children with CD often have marked growth retardation and EEN is one of the most efficacious treatment options to induce catch-up growth in these patients. There is convincing data indicating that EN is highly efficacious when given on an exclusive basis, while the use of partial EN is markedly less effective to induce remission in active Crohn's disease as compared to exclusive EN. Recently, it was suggested that exclusive EN has a dominant effect on the intestinal microbiota, which contributes to the induction of remission. There exists several strategies to maintain remission in children with CD, but there is no clear consensus on which maintenance treatment to follow. There are some indicators to believe that enteral nutritional therapy might play also a significant role as maintenance therapy for CD. Given the fact that many centers use a top-down approach with the introduction of immunosuppressors and/or biologics at/or shortly after diagnosis, the investigators wanted to test the possibility of a treatment option to efficiently maintain remission with less (or no) side effects based on enteral nutrition to avoid the early use of immunosuppressors.

It's a French multicenter, prospective, randomized study with PROBE (prospective randomized open blind end-point) evaluation. Randomization will be performed in a blinded and centralized manner, allocating patients to one of the two treatment groups :

* ARM A : Cyclic exclusive MODULEN IBD for 2 weeks every 8 weeks

* ARM B: MODULEN IBD supplementation (25% of caloric requirements) alone

A Physician not involved in the study design and blinded to the treatment arm will perform the evaluation of the patients during each study visit.

A total of four visits (including final visit) are scheduled for this trial over a period of 12 months at a rhythm of every three months (+/- 2 weeks) for all patients. The study visit will happen during scheduled routine visits, necessary for the routine care of CD patients. Each visit comprises a routine clinical evaluation. The assessment of maintenance of remission is particularly important (wPCDAI\<12.5 points), a routine lab analysis including fecal calprotectin is required at each visit. In addition, all relevant medical or other events will be recorded. Only for patients who participate in the annex studies an additional stool sample (microbial analysis) is required. At M9 visit, follow-up endoscopy (M12+/- 6weeks) and entero-MRI (M12+/- 6 weeks) will be programmed as part of the routine surveillance of patients on maintenance therapy, allowing to adjust treatment in the following if necessary. Compliance to treatment will be monitored by recordings of daily MODULEN IBD intake during 2 week periods on the E-system. A quality of life E-questionnaire will be filled out one day prior to each visit.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • 6-18 years
  • Confirmed Crohn's disease (L1, L2, L3+/- L4a/b)
  • new-onset disease or acute relapse treated with enteral nutrition
  • responding to induction therapy with exclusive enteral nutrition with complete clinical remission at inclusion visit (wPCDAI<12.5)
  • completed cycle of induction therapy of at least 6 weeks (6-12 weeks)
  • biological treatment by Remicade has to be stopped at least 8 weeks prior to inclusion
  • "wash out" of corticosteroids, immunosuppressors and treatment by Humira of minimally 4 weeks prior to inclusion
  • 5-ASA and derivates have to be stopped at least at screening visit
  • Antibiotics must be stopped at least 2 weeks prior to inclusion
  • Informed and signed consent
Exclusion Criteria
  • Patients with B2 or B3 disease behavior (intestinal/colonic stenosis (including ileo-caecal valve), intrabdominal abscess, fistulizing disease)
  • Patients not in remission on induction therapy (wPCDAI>12.5)
  • Patients with isolated and severe perianal disease
  • Patients requiring surgical therapy at inclusion
  • Ongoing steroid medication
  • Ongoing immunosuppressor or biologics therapy
  • No informed consent
  • Currently participating or having participated in another interventional clinical trial during the last 4 weeks prior to the beginning of this study

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cyclic exclusive MODULEN IBDMODULEN IBDCyclic exclusive MODULEN IBD for 2 weeks every 8 weeks
MODULEN IBD supplementation (25% of caloric requirements)MODULEN IBDMODULEN IBD supplementation (25% of caloric requirements) alone A Physician not involved in the study design and blinded to the treatment arm will perform the evaluation of the patients during each study visit.
Primary Outcome Measures
NameTimeMethod
The first relapse12 months

Assessed with wPCDAI

Secondary Outcome Measures
NameTimeMethod
Calprotectinuntil month12

Fecal sample

Growth patternUntil Month 12

Z-Score

Endoscopic remissionmonth 12

CDEIS

Transmural healingMonth 12

MRI

Time to the first relapseuntil month 12

Assessed with wPCDAI, CDAI, PGA

Clinical remission12 months

Assessed with wPCDAI, CDAI, PGA

Variation of wPCDAI,until month12

Assessed with wPCDAI

Quality of life analysisUntil Month 12

E-questionnaire

Trial Locations

Locations (1)

Hôpital Necker - Enfants Malades

🇫🇷

Paris, France

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