CEASE: Crohn Disease Exclusion Diet After Single Medication De-escalation

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02472457
• Collaborator: Wolfson Medical Center (Other)
• Enrollment: 19
• Location: 1
• Arms: 2
• Actual Duration (Months): 61
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine whether pediatric Crohn Disease (CD) patients in long-standing remission remain in remission longer after stopping medications if they follow the Crohn's Disease Exclusion Diet (CDED). The hypothesis is that subjects on the CDED will have longer time-to-relapse as opposed to those on an unrestricted diet.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Other: Crohn Disease Exclusion Diet; Other: Free Diet	N/A

Detailed Description

Crohn disease (CD) is an idiopathic, chronic, relapsing and remitting inflammatory condition of the gastrointestinal tract with a high risk for complications and need for surgical interventions, particularly in children. Immunomodulators and biologic therapies are effective at inducing and maintaining remission in pediatric CD, yet there is no proven strategy for reducing exposure to medications once sustained remission has been achieved. Diet has been proven to impact disease activity in CD and may allow for sustained drug-free remission. The primary objective of this study is to determine whether pediatric CD patients in long-standing remission remain in remission longer after stopping medications if they follow the Crohn's Disease Exclusion Diet (CDED). The hypothesis is that subjects on the CDED will have longer time-to-relapse as opposed to those on an unrestricted diet.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Biologic and Immunomodulator Withdrawal in Pediatric Crohn Disease With Deep Clinical Remission Using the Crohn Disease Exclusion Diet
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Free Diet No dietary restrictions	Other: Free Diet; This diet contains no restrictions.; Other Names: Placebo
Active Comparator: Crohn Disease Exclusion Diet The CDED is a palatable diet that excludes foods suspected to have a role in intestinal inflammation.	Other: Crohn Disease Exclusion Diet; The CDED is divided into 4 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase I, and weeks 25-52 maintenance phase II.

Outcome Measures

Primary Outcome Measures

1. Sustained Relapse-free Remission [At 52 weeks following enrollment]

   Remission defined by the Pediatric Crohn Disease Activity Index, C-reactive protein, and stool calprotectin

Secondary Outcome Measures

1. Time-to-relapse [Up to 104 weeks]

   Remission defined by the Pediatric Crohn Disease Activity Index, C-reactive protein, and stool calprotectin

2. Microbial Composition of Gastrointestinal Tract (Types and Quantities of Microorganisms) [6 weeks]

   Change in the microbial composition of the stool, mouth and rectum from baseline to 6 weeks

3. Microbial Composition of Gastrointestinal Tract (Types and Quantities of Microorganisms) [52 weeks]

   Change in the microbial composition of the stool, mouth and rectum from baseline to 52 weeks

Other Outcome Measures

1. Dietary Compliance [Up to 52 weeks]

   Using modified Medication Adherence Rating Scale (MARS) questionnaire

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with a diagnosis of Crohn Disease using the Revised Porto criteria who will be withdrawing from biologic or immunomodulator monotherapy as part of clinical care.

• Normal Growth Velocity, or Tanner 5

• Steroid-free Remission (Pediatric Crohn Disease Activity Index Score <10 without the height component) for at least 12 months prior to enrollment

• Colonoscopy during the preceding 3 months with complete mucosal healing or only few aphthous ulcerations located in one segment

• Stool calprotectin <250µg/g during the preceding 3 months

• Parental/guardian permission (informed consent) and, if appropriate, child assent.

Exclusion Criteria:

• Discontinuation of biologic or immunomodulator therapy by the subject without the approval of the primary gastroenterologist.

• Those subjects who in the judgment of the investigative team are unable to complete the study endpoints.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia
• Wolfson Medical Center

Investigators

• Principal Investigator: Ronen Stein, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 10, 2019

More Information

Publications

• Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease. Inflamm Bowel Dis. 2014 Aug;20(8):1353-60. doi: 10.1097/MIB.0000000000000110.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT02472457
• Other Study ID Numbers: 14-011628
• First Posted: Jun 15, 2015
• Last Update Posted: Oct 20, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Crohn Disease

Study Results

Participant Flow

Arm/Group Title	Free Diet	Crohn Disease Exclusion Diet
Arm/Group Description	No dietary restrictions Free Diet: This diet contains no restrictions.	The CDED is a palatable diet that excludes foods suspected to have a role in intestinal inflammation. Crohn Disease Exclusion Diet: The CDED is divided into 4 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase I, and weeks 25-52 maintenance phase II.
Period Title: Overall Study
STARTED	8	11
COMPLETED	8	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Free Diet	Crohn Disease Exclusion Diet	Total
Arm/Group Description	No dietary restrictions Free Diet: This diet contains no restrictions.	The CDED is a palatable diet that excludes foods suspected to have a role in intestinal inflammation. Crohn Disease Exclusion Diet: The CDED is divided into 4 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase I, and weeks 25-52 maintenance phase II.	Total of all reporting groups
Overall Participants	8	10	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.5 (3.6)	16.0 (2.2)	16.2 (2.8)
Sex: Female, Male (Count of Participants)
Female	4 50%	2 20%	6 33.3%
Male	4 50%	8 80%	12 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 100%	10 100%	18 100%
Region of Enrollment (participants) [Number]
United States	7 87.5%	6 60%	13 72.2%
Israel	1 12.5%	4 40%	5 27.8%

Outcome Measures

1. Primary Outcome

Title	Sustained Relapse-free Remission
Description	Remission defined by the Pediatric Crohn Disease Activity Index, C-reactive protein, and stool calprotectin
Time Frame	At 52 weeks following enrollment

Outcome Measure Data

Analysis Population Description

1 participant in the free diet group followed the specific carbohydrate diet and was in remission at 52 weeks. 1 participant in the CDED group withdrew prior to 52 weeks.

Arm/Group Title	Free Diet	Crohn Disease Exclusion Diet
Arm/Group Description	No dietary restrictions Free Diet: This diet contains no restrictions.	The CDED is a palatable diet that excludes foods suspected to have a role in intestinal inflammation. Crohn Disease Exclusion Diet: The CDED is divided into 4 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase I, and weeks 25-52 maintenance phase II.
Measure Participants	8	9
Count of Participants [Participants]	6 75%	5 50%

2. Secondary Outcome

Title	Time-to-relapse
Description	Remission defined by the Pediatric Crohn Disease Activity Index, C-reactive protein, and stool calprotectin
Time Frame	Up to 104 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Microbial Composition of Gastrointestinal Tract (Types and Quantities of Microorganisms)
Description	Change in the microbial composition of the stool, mouth and rectum from baseline to 6 weeks
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Microbial Composition of Gastrointestinal Tract (Types and Quantities of Microorganisms)
Description	Change in the microbial composition of the stool, mouth and rectum from baseline to 52 weeks
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Dietary Compliance
Description	Using modified Medication Adherence Rating Scale (MARS) questionnaire
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	52 weeks
Adverse Event Reporting Description	Adverse event information was obtained via chart review and trial visits
Arm/Group Title	Free Diet		Crohn Disease Exclusion Diet
Arm/Group Description	No dietary restrictions Free Diet: This diet contains no restrictions.		The CDED is a palatable diet that excludes foods suspected to have a role in intestinal inflammation. Crohn Disease Exclusion Diet: The CDED is divided into 4 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase I, and weeks 25-52 maintenance phase II.
All Cause Mortality
	Free Diet		Crohn Disease Exclusion Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Serious Adverse Events
	Free Diet		Crohn Disease Exclusion Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Free Diet		Crohn Disease Exclusion Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.