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

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ClinicalTrials.gov Identifier: NCT04777656
Recruitment Status : Recruiting
First Posted : March 2, 2021
Last Update Posted : November 1, 2022
Sponsor:
Collaborators:
URC-CIC Paris Descartes Necker Cochin
MICALIS Institute
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Crohn's Disease Dietary Supplement: Phase1 : CDED/Modulen™IBD® + Maintenance therapy Dietary Supplement: Phase2 and 3 : Phase 3

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 26, 2022
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : November 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: CDED/Modulen™IBD®
Strategy combining CD exclusion diet plus Modulen™IBD® on top of ongoing maintenance therapy.
Dietary Supplement: Phase1 : CDED/Modulen™IBD® + Maintenance therapy
from D0 until M2: Phase 1 (2 months run-in phase with CDED protocol + maintenance therapy, with the exception of corticosteroid that have to be tapered and stopped until M2.)

Dietary Supplement: Phase2 and 3 :
from M2 until M4 CDED phase 2 (introduction of a selected number of additional food). From M4 until end of the study CDED phase 3 (enlargement of number of additional foods and allowance of some initially excluded foods).
Other Name: CDED/Modulen™IBD® + Maintenance therapy

Active Comparator: Unrestricted food access
Stop CDED and Modulen™IBD®, but continue maintenance therapy with unrestricted food access.
Dietary Supplement: Phase1 : CDED/Modulen™IBD® + Maintenance therapy
from D0 until M2: Phase 1 (2 months run-in phase with CDED protocol + maintenance therapy, with the exception of corticosteroid that have to be tapered and stopped until M2.)

Not randomized
Patient not in remission at M2 or refusing randomisation
Dietary Supplement: Phase1 : CDED/Modulen™IBD® + Maintenance therapy
from D0 until M2: Phase 1 (2 months run-in phase with CDED protocol + maintenance therapy, with the exception of corticosteroid that have to be tapered and stopped until M2.)




Primary Outcome Measures :
  1. Relapse from randomization until M12 [ Time Frame: 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 :
  1. Change of wPCDAI from baseline to M2 [ Time Frame: 2 months ]
  2. Change of fecal calprotectin values from baseline to M2 [ Time Frame: 2 months ]
  3. Clinical remission at M2 [ Time Frame: 2 months ]
    Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)

  4. Deep remission at M2 [ Time Frame: 2 months ]
    Defined as wPCDAI ≤12.5 and normal CRP within normal lab range) and normal fecal calprotectin ((<250µg/g)

  5. Physician global assessment (PGA) from baseline to M2 [ Time Frame: 2 months ]
    Crohn's Disease activity assessed as remission - weak - moderate - severe

  6. Mucosal healing at M2 [ Time Frame: 2 months ]
    absence of any ulcerations (including aphthae)

  7. Endoscopic response at M2 [ Time Frame: 2 months ]
    Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline

  8. Change of MRI from baseline to M2 [ Time Frame: 2 months ]
    Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from baseline to M2

  9. CDED tolerance rate at M2 [ Time Frame: 2 months ]
    serious and non serious adverse events

  10. CDED compliance rate at M2 [ Time Frame: 2 months ]
  11. Change of intestinal microbiome composition from baseline to M2 [ Time Frame: 2 months ]
  12. Clinical remission [ Time Frame: At 4 months, 6 months, 9 months and 12 months ]
    Defined as wPCDAI ≤12.5 and normal CRP (≤1.5 fold upper normal range)

  13. Deep remission [ Time Frame: 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)

  14. Relapse [ Time Frame: 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

  15. Physician global assessment (PGA) [ Time Frame: At 4 months, 6 months, 9 months and 12 months ]
    Crohn's Disease activity assessed as remission - weak - moderate - severe

  16. Mucosal Healing at M12 [ Time Frame: 12 months ]
    Absence of any ulcerations (including aphthae)

  17. Endoscopic response at M12 [ Time Frame: 12 months ]
    Decrease of Crohn's Disease Endoscopic Index Score (CDEIS) ≥ 50% from baseline

  18. Change of MRI from M2 to M12 [ Time Frame: 12 months ]
    Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease score from M2 to M12

  19. CDED tolerance rate at M12 [ Time Frame: 12 months ]
    Serious and non serious adverse events

  20. CDED compliance rate at M12 [ Time Frame: 12 months ]
  21. Change of Intestinal microbiome composition [ Time Frame: At 4 months, 6 months, 9 months, 12 months ]
  22. Change of quality of life IMPACT-3 from inclusion until 12 months [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04777656


Contacts
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Contact: Franck Ruemmele, MD, PhD +33 (0)1 44 49 25 16 frank.ruemmele@aphp.fr
Contact: Prissile Bakouboula, PhD +33 (0)1 71 19 64 94 prissile.bakouboula@aphp.fr

Locations
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France
Hôpital Femme mère enfant, CHU Lyon - Service Hépato-gastroentérologie et Nutrition pédiatrique Recruiting
Bron, France, 69677
Contact: Rémi Duclaux-Loras, MD, PhD    +33-4-72-35-70-50    remi.duclaux-loras@chu-lyon.fr   
CHU Caen Normandie - Service de Gastroentérologie pédiatrique Recruiting
Caen, France, 14033
Contact: Claire Dupont-Lucas, MD, PhD    +33-2-31-27-25-94    dupont-c@chu-caen.fr   
Hôpital de la Timone, AP-HM - Service de Gastroentérologie pédiatrique Recruiting
Marseille, France, 13385
Contact: Céline Roman, MD, PhD    +33-4-91-38-83-83    celine.roman@ap-hm.fr   
Hôpital Necker-Enfants malades - Service de Gastroentérologie pédiatrique Recruiting
Paris, France, 75015
Contact: Franck Ruemmele, MD, PhD    +33 (0)1 44 49 25 16    frank.ruemmele@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
URC-CIC Paris Descartes Necker Cochin
MICALIS Institute
Investigators
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Principal Investigator: Franck Ruemmele, MD, PhD Assistance Publique - Hôpitaux de Paris
Publications:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04777656    
Other Study ID Numbers: APHP200010
2020-A02569-30 ( Other Identifier: ID-RCB )
First Posted: March 2, 2021    Key Record Dates
Last Update Posted: November 1, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Crohn's disease
Recurrent inflammatory disorder
Immunomodulators
Biologics
Exclusive Enteral Nutrition
Crohn's disease exclusion diet (CDED)
Modulen™IBD®
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases