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Exclusion Diet vs corticosteroIds in patientS With activE Crohn's Disease (PARADISE)

Primary Purpose

Crohn Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Crohn's disease exclusion diet (CDED)
Oral prednisolone
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn Disease focused on measuring Crohn Disease, Diet, Corticosteroids

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged 16 to 70 years,
  • With mild to moderate, luminal, active CD, defined by a CDAI of 150 to 350,
  • Involving the small bowel, and/or the colon
  • Not treated with corticosteroids at baseline
  • Patent small bowel as assessed by the patency capsule
  • Active endoscopic lesions, as defined by Lewis score ≥ 225 in the small bowel and/or SES-CD≥ 4 in the colon. The eligibility of the patient will be determined by the site investigator and a central reader.
  • Informed consent to participate in this study. In patients from France and Israel who are aged less than 18: parents' informed consent to participate in this study (parents' agreement is not required in patients aged 16 to 18 in the Netherlands)
  • Affiliation to social security or any health insurance

Exclusion Criteria:

  • Inability to follow the CDED during 16 weeks.
  • Prior intolerance to corticosteroids.
  • Ongoing infections, evolving virus diseases.
  • Live vaccines.
  • Psychotic state not controlled by treatment.
  • Arthritis or uveitis as main presenting symptoms.
  • Patients with severe and/or predominant rectal or perianal disease.
  • Heavy smokers (more than 10 cigarettes per day).
  • Infliximab, adalimumab, methotrexate or azathioprine initiated less than 3 months before inclusion in this trial.
  • Vedolizumab, ustekinumab initiated less than 6 months before inclusion in this trial.
  • Change in methotrexate, azathioprine, infliximab, adalimumab, vedolizumab or ustekinumab dosage less than 3 months before inclusion.
  • Pregnant or lactating women.
  • Patients already included in a biomedical research other than an observational study (e.g. registry, cohort, biobank).
  • Severe pubertal delay (Tanner 1 or Tanner 2) and/or height velocity z-score < 2.5 and/or Bone mineral density z-score (hip or lumbar spine) <2.5.
  • Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under sections L.3212-1 et L.3213-1 and persons admitted to a health or social institution for purposes other than research (L.1121-6)

Sites / Locations

  • Gastroenterology department
  • Department of Gastroenterology & Hepatology (MDL), Amsterdam UMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Crohn's disease exclusion diet (CDED)

Steroids

Arm Description

16-week course of Crohn's disease exclusion diet (CDED) and Partial Enteral Nutrition.

oral prednisolone at an initial dose of 40 to 60 mg/day.

Outcomes

Primary Outcome Measures

Endoscopic response W16
The primary endpoint is the endoscopic response at week 16, assessed by Panenteric capsule (PillCam Crohn's capsule) using centralized, anonymous and blinded reading of PCC. The response is defined as a single binary endpoint according to the initial strata of the patient: Small bowel Crohn's diseAse (CD) : decrease of the Lewis score of at least 50% compared to baseline values Colonic CD : decrease of SES-CD of at least 50% compared to baseline values Small bowel and colonic CD : decrease of the Lewis score of at least 50% AND decrease of SES-CD of at least 50% compared to baseline values. Lewis score : Gralnek IM, Defranchis R, et al. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther 2008; 27: 146-154. SES-CD : Daperno M, D'Haens G, et al . Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc 2004; 60 (4): 505-512.

Secondary Outcome Measures

Rate of Clinical remission
Crohn's disease activity index (CDAI) <150. CDAI will be measured by the investigator on the basis of prospective questionnaires filled in by patients during the week preceding each visit. Best, William R., Jack M. Becktel, John W. Singleton, and Fred Kern Jr. "Development of a Crohn's disease activity index: National Cooperative Crohn's Disease Study." Gastroenterology 70, no. 3 (1976): 439-444.
Rate of Clinical response
Decrease of at least 70 points in Crohn's disease activity index (CDAI) compare to CDAI baseline.
Rate of Need for further therapeutic intervention
Need for further therapeutic intervention (i.e., steroids, immunosuppressants, new biologic or surgery) between week 13 and 48
Decrease of fecal calprotectin concentration
Decrease of fecal calprotectin of at least 50% compared to baseline at week 16 and 48
Rate of Fecal calprotectin below thresholds
Fecal calprotectin of less than 250 μg/g, less than 100 μg/g and less than 50 μg/g at week 16.
Rate of normal CRP concentration
CRP serum level <5 mg/L.
Rate of Endoscopic remission
Endoscopic remission as defined as Lewis score <135 in the small bowel and/or Simple Endoscopic Score for Crohn Disease (SES-CD) <4 in the colon, without further therapeutic intervention (surgery, biologics or dietary intervention) at week 16. Dias de Castro, F., Pedro Boal Carvalho, Sara Monteiro, Bruno Rosa, João Firmino-Machado, Maria João Moreira, and José Cotter. "Lewis score-prognostic value in patients with isolated small bowel Crohn's disease." Journal of Crohn's and Colitis 9, no. 12 (2015): 1146-1151. Daperno, Marco, Geert D'Haens, Gert Van Assche, Filip Baert, Philippe Bulois, Vincent Maunoury, Raffaello Sostegni et al. "Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD." Gastrointestinal endoscopy 60, no. 4 (2004): 505-512.
Rate of Endoscopic response
Endoscopic response and remission graded by Eliakim score at week 16. Eliakim, Rami, et al. "A novel PillCam Crohn's capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn's disease." United European gastroenterology journal 8.5 (2020): 544-551.
Gut microbiota composition
Gut microbiota composition at week 6 and week 16. The endpoint consist in the rate of the diffrent microorganisms present in the gut.
Value of adherence by Medication Adherence Report Scale
Medication Adherence Report Scale (MARS) at week 1, 9 and 16. Chan, Amy Hai Yan, Rob Horne, Matthew Hankins, and Claudia Chisari. "The medication adherence report scale: a measurement tool for eliciting patients' reports of nonadherence." British Journal of Clinical Pharmacology 86, no. 7 (2020): 1281-1288.
Rate of adherence using food diaries
Adherence evaluate as binuary outcome evaluated using food diaries at week 1, 9 and 16
Value of Quality of life
Quality of life will be assessed by short inflammatory bowel disease questionnaire (IBDQ) at week 3, 6 and 16. Irvine, E. J., Q. Zhou, and A. K. Thompson. "The Short Inflammatory Bowel Disease Questionnaire: A Quality of Life Instrument for Community Physicians Managing Inflammatory Bowel Disease." American Journal of Gastroenterology (Springer Nature) 91.8 (1996).
Value Work
Work productivity and activity will be assessed by thework productivity and activity impairment questionnaire (WPAI) at 6 and 16. Reilly, Margaret C., Arthur S. Zbrozek, and Ellen M. Dukes. "The validity and reproducibility of a work productivity and activity impairment instrument." Pharmacoeconomics 4.5 (1993): 353-365.

Full Information

First Posted
February 28, 2022
Last Updated
March 9, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT05284136
Brief Title
Exclusion Diet vs corticosteroIds in patientS With activE Crohn's Disease
Acronym
PARADISE
Official Title
Prospective rAndomized Controlled tRial of Crohn's diseAse Exclusion Diet vs corticosteroIds in patientS With activE Crohn's Disease - PARADISE
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
April 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Crohn's disease exclusion diet (CDED) is a whole-food diet coupled with partial enteral nutrition. The main objective of this trial is to assess whether CDED is superior to corticosteroids, in terms of endoscopic response, in patients active CD. The primary endpoint is endoscopic response at week 16, without corticosteroids or further therapeutic intervention, assessed by a centralized, anonymous and blinded, double lecture panel of panenteric PillCam Crohn's Capsule. This is a multicentre, open-label, comparative, randomized, 2:1, controlled, single-blind, superiority trial. Patients included are aged 16 to 70 years, have mild to moderate, luminal, active CD, and have active endoscopic lesions. Eighty patients will be randomized between CDED (n=56) and corticosteroids (n=24) in centres in France, Israel and the Netherlands.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Crohn Disease, Diet, Corticosteroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Crohn's disease exclusion diet (CDED)
Arm Type
Experimental
Arm Description
16-week course of Crohn's disease exclusion diet (CDED) and Partial Enteral Nutrition.
Arm Title
Steroids
Arm Type
Active Comparator
Arm Description
oral prednisolone at an initial dose of 40 to 60 mg/day.
Intervention Type
Dietary Supplement
Intervention Name(s)
Crohn's disease exclusion diet (CDED)
Intervention Description
16-week course of CDED+Partial Enteral Nutrition. During the first 6 weeks (phase 1 of CDED), patients will be prescribed the CDED and oral Modulen 1 liter (1000kcal) daily. Between week 6 and 16 (phase 2 of CDED), patients will be prescribed CDED and oral Modulen (500 mL).
Intervention Type
Drug
Intervention Name(s)
Oral prednisolone
Intervention Description
oral prednisolone at an initial dose of 40 to 60 mg/day (or 1 mg/kg for those patients who weigh less than 40 kg), with a fixed, tapering regimen such that patients should be off steroids by the last day of week 12. Increases in steroid dose during tapering of corticosteroids is allowed but if the patient receives steroids (other than hydrocortisone for adrenal insufficiency) after week 12, he/she is in failure.
Primary Outcome Measure Information:
Title
Endoscopic response W16
Description
The primary endpoint is the endoscopic response at week 16, assessed by Panenteric capsule (PillCam Crohn's capsule) using centralized, anonymous and blinded reading of PCC. The response is defined as a single binary endpoint according to the initial strata of the patient: Small bowel Crohn's diseAse (CD) : decrease of the Lewis score of at least 50% compared to baseline values Colonic CD : decrease of SES-CD of at least 50% compared to baseline values Small bowel and colonic CD : decrease of the Lewis score of at least 50% AND decrease of SES-CD of at least 50% compared to baseline values. Lewis score : Gralnek IM, Defranchis R, et al. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther 2008; 27: 146-154. SES-CD : Daperno M, D'Haens G, et al . Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc 2004; 60 (4): 505-512.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Rate of Clinical remission
Description
Crohn's disease activity index (CDAI) <150. CDAI will be measured by the investigator on the basis of prospective questionnaires filled in by patients during the week preceding each visit. Best, William R., Jack M. Becktel, John W. Singleton, and Fred Kern Jr. "Development of a Crohn's disease activity index: National Cooperative Crohn's Disease Study." Gastroenterology 70, no. 3 (1976): 439-444.
Time Frame
Week 16 and Week 48
Title
Rate of Clinical response
Description
Decrease of at least 70 points in Crohn's disease activity index (CDAI) compare to CDAI baseline.
Time Frame
Week 16 and Week 48
Title
Rate of Need for further therapeutic intervention
Description
Need for further therapeutic intervention (i.e., steroids, immunosuppressants, new biologic or surgery) between week 13 and 48
Time Frame
Week 48
Title
Decrease of fecal calprotectin concentration
Description
Decrease of fecal calprotectin of at least 50% compared to baseline at week 16 and 48
Time Frame
Week 16 and Week 48
Title
Rate of Fecal calprotectin below thresholds
Description
Fecal calprotectin of less than 250 μg/g, less than 100 μg/g and less than 50 μg/g at week 16.
Time Frame
Week 16
Title
Rate of normal CRP concentration
Description
CRP serum level <5 mg/L.
Time Frame
Week 16 and Week 48
Title
Rate of Endoscopic remission
Description
Endoscopic remission as defined as Lewis score <135 in the small bowel and/or Simple Endoscopic Score for Crohn Disease (SES-CD) <4 in the colon, without further therapeutic intervention (surgery, biologics or dietary intervention) at week 16. Dias de Castro, F., Pedro Boal Carvalho, Sara Monteiro, Bruno Rosa, João Firmino-Machado, Maria João Moreira, and José Cotter. "Lewis score-prognostic value in patients with isolated small bowel Crohn's disease." Journal of Crohn's and Colitis 9, no. 12 (2015): 1146-1151. Daperno, Marco, Geert D'Haens, Gert Van Assche, Filip Baert, Philippe Bulois, Vincent Maunoury, Raffaello Sostegni et al. "Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD." Gastrointestinal endoscopy 60, no. 4 (2004): 505-512.
Time Frame
Week 16
Title
Rate of Endoscopic response
Description
Endoscopic response and remission graded by Eliakim score at week 16. Eliakim, Rami, et al. "A novel PillCam Crohn's capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn's disease." United European gastroenterology journal 8.5 (2020): 544-551.
Time Frame
Week 16
Title
Gut microbiota composition
Description
Gut microbiota composition at week 6 and week 16. The endpoint consist in the rate of the diffrent microorganisms present in the gut.
Time Frame
Week 6 and Week 16
Title
Value of adherence by Medication Adherence Report Scale
Description
Medication Adherence Report Scale (MARS) at week 1, 9 and 16. Chan, Amy Hai Yan, Rob Horne, Matthew Hankins, and Claudia Chisari. "The medication adherence report scale: a measurement tool for eliciting patients' reports of nonadherence." British Journal of Clinical Pharmacology 86, no. 7 (2020): 1281-1288.
Time Frame
Week 1, Week 9 and Week 16
Title
Rate of adherence using food diaries
Description
Adherence evaluate as binuary outcome evaluated using food diaries at week 1, 9 and 16
Time Frame
Week 1, Week 9 and Week 16
Title
Value of Quality of life
Description
Quality of life will be assessed by short inflammatory bowel disease questionnaire (IBDQ) at week 3, 6 and 16. Irvine, E. J., Q. Zhou, and A. K. Thompson. "The Short Inflammatory Bowel Disease Questionnaire: A Quality of Life Instrument for Community Physicians Managing Inflammatory Bowel Disease." American Journal of Gastroenterology (Springer Nature) 91.8 (1996).
Time Frame
Week 3, Week 6 and Week 16
Title
Value Work
Description
Work productivity and activity will be assessed by thework productivity and activity impairment questionnaire (WPAI) at 6 and 16. Reilly, Margaret C., Arthur S. Zbrozek, and Ellen M. Dukes. "The validity and reproducibility of a work productivity and activity impairment instrument." Pharmacoeconomics 4.5 (1993): 353-365.
Time Frame
Week 6 and Week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged 16 to 70 years, With mild to moderate, luminal, active CD, defined by a CDAI of 150 to 350, Involving the small bowel, and/or the colon Not treated with corticosteroids at baseline Patent small bowel as assessed by the patency capsule Active endoscopic lesions, as defined by Lewis score ≥ 225 in the small bowel and/or SES-CD≥ 4 in the colon. The eligibility of the patient will be determined by the site investigator and a central reader. Informed consent to participate in this study. In patients from France and Israel who are aged less than 18: parents' informed consent to participate in this study (parents' agreement is not required in patients aged 16 to 18 in the Netherlands) Affiliation to social security or any health insurance Exclusion Criteria: Inability to follow the CDED during 16 weeks. Prior intolerance to corticosteroids. Ongoing infections, evolving virus diseases. Live vaccines. Psychotic state not controlled by treatment. Arthritis or uveitis as main presenting symptoms. Patients with severe and/or predominant rectal or perianal disease. Heavy smokers (more than 10 cigarettes per day). Infliximab, adalimumab, methotrexate or azathioprine initiated less than 3 months before inclusion in this trial. Vedolizumab, ustekinumab initiated less than 6 months before inclusion in this trial. Change in methotrexate, azathioprine, infliximab, adalimumab, vedolizumab or ustekinumab dosage less than 3 months before inclusion. Pregnant or lactating women. Patients already included in a biomedical research other than an observational study (e.g. registry, cohort, biobank). Severe pubertal delay (Tanner 1 or Tanner 2) and/or height velocity z-score < 2.5 and/or Bone mineral density z-score (hip or lumbar spine) <2.5. Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under sections L.3212-1 et L.3213-1 and persons admitted to a health or social institution for purposes other than research (L.1121-6)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Franck Carbonnel, MD-PHD
Phone
142499742
Ext
33
Email
fcarbonnel7@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
matthieu Resche-Rigon, MD-PHD
Phone
142499747
Ext
33
Email
matthieu.resche-rigon@u-paris.fr
Facility Information:
Facility Name
Gastroenterology department
City
Le Kremlin Bicetre
ZIP/Postal Code
94
Country
France
Facility Name
Department of Gastroenterology & Hepatology (MDL), Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marloes Zwart, MD
Phone
20 5661242
Ext
31
Email
m.zwart2@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Marjolijn Duijvestein, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Exclusion Diet vs corticosteroIds in patientS With activE Crohn's Disease

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