Back to resultsDiet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease (DIETOMICS-CD)
Primary Purpose
Crohn's Disease
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Modified Exclusive Enteral Nutrition
Crohn's Disease Exclusion Diet
Partial Enteral Nutrition
Standard Exclusive Enteral Nutrition
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's Disease, Pediatric, Exclusive Enteral Nutrition, Diet, Microbiome
Eligibility Criteria
Inclusion criteria:
- Established diagnosis of Crohn's disease.
- Patients with mild to severe active Crohn's disease (15≤PCDAI≤47.5)
- Ages 8-18
- Duration of disease ≤ 36 months
- Active inflammation (CRP≥>0.6 mg /dL or ESR≥>20 or Calprotectin≥>200 mcg/gr within the past 3 weeks) during screening
- Patients with B1, P0 uncomplicated disease at enrollment
- Patients with disease defined as L1, L4, L3 or L2 limited to cecum, ascending or transverse colon or L2 with left sided disease with terminal ileum or small bowel involvement in the past by the Paris classification (patients with macroscopic disease)
- Signed informed consent
Exclusion Criteria:
- Patients with very mild disease (PCDAI 12.5 -15) or very severe disease (PCDAI >47.5)
- Pregnancy
- Patients who have disease confined to the colon involving the descending colon, rectum or sigmoid colon and no prior history of small bowel involvement
- Patients who have active extra intestinal disease (such as Arthritis, Uveitis, Pyoderma Gangrenosum, Erythema Nodosum etc.)
- Patients with complicated disease (B2, B3)
- Patients who recently onset use of an immunomodulator <8 weeks, or dose change in past 8 weeks.
- Patients with current use of biologics, or use in last 8 weeks or current use of systemic steroids
- Patients who have active perianal disease ( active fistula or abscess)
- Patients who have positive stool cultures with relevant pathogens,, or positive tests for parasites or C. difficile. Stool tests are mandatory only if diarrhea is present.
- Patients with fever > 38.3
- Documented milk protein allergy
Sites / Locations
- Dr. Eytan Wine,
- Johan Van Limbergen
- Dr Sally Lawrence
- Dr. Séamus Hussey
- The E. Wolfson.Medical Center
- Dr. Francisco Javier Martin Carpi
- Dr. Víctor Manuel Navas López
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group 1
Group 2
Arm Description
Modified Exclusive Enteral Nutrition including two weeks of Exclusive Enteral Nutrition (EEN) using Modulen followed by Partial Enteral Nutrition (PEN) along with the Crohn's Disease Exclusion Diet (CDED) phases 2 & 3 for 24 weeks
Standard Exclusive Enteral Nutrition for 8 weeks using Modulen, followed by free diet with gradual reduction of Modulen to 25% of energy needs by week 24.
Outcomes
Primary Outcome Measures
ITT, steroid free Clinical remission (defined as Pediatric Crohn's Disease Activity Index (PCDAI)<10) at week 14
Sustained remission with EEN Vs CDED+PEN
Secondary Outcome Measures
ITT steroid free remission at week 8
Induction of remission
Microbiome composition difference between groups at week 14
Assessment of microbiome composition and metabolomics
3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment
Mucosal healing assessment
Steroid and biologic free sustained remission at week 24.
Remission achieved and maintained without additional therapy
Need for additional treatment to achieve remission by week 14
Remission achieved without additional therapy
Mucosal healing as assessed by MRE in dietary responsive disease at week 52
Mucosal healing
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02843100
Brief Title
Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease
Acronym
DIETOMICS-CD
Official Title
Modified Exclusive Enteral Nutrition With the Crohn's Disease Exclusion Diet for Induction and Maintenance of Remission and Re-biosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
May 29, 2022 (Actual)
Study Completion Date
May 29, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Arie Levine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The modified-Exclusive Enteral Nutrition (mEEN) is an open label randomized controlled trial in mild to severe Crohn's Disease patients. The purpose of this study is to determine whether induction of remission and maintenance of remission can be achieved with a new dietary strategy that involves only 2 weeks of Exclusive Enteral Nutrition (EEN) with Modulen and 12 weeks of an exclusion diet involving selected table foods. This novel approach will be compared to the gold standard dietary regime involving 8 weeks of EEN.
Detailed Description
Rational: Exclusive enteral nutrition (EEN) is an established but difficult to perform method for induction of remission and cannot be used for maintenance of remission. It entails drinking only liquid formula for 8 weeks. Refusal to use or to adhere to this therapy is not uncommon and leads to use of other non- dietary strategies in children including steroids and immunosuppression. The Crohn's Disease Exclusion Diet (CDED) with partial enteral nutrition has been shown to be effective for children with mild to moderate disease. The investigators have developed a maintenance strategy using the CDED.
Objectives: To prove that induction of remission and maintenance of remission can be achieved with a new dietary strategy that involves only 2 weeks of EEN with Modulen and 12 weeks of an exclusion diet involving selected table foods.
Methods: Open label randomized controlled pilot trial comparing two weeks of EEN followed by the CDED and Partial Enteral Nutrition (PEN), to 8 weeks of EEN followed by PEN with free diet. The study will include a control group of healthy children for microbiome studies.
Population: Age 8-18 years with mild to severe active Crohn's disease defined as 15≤Pediatric Crohn's Disease Activity Index (PCDAI)<47.5.
Time frame: The induction of remission phase will last 8 weeks followed by maintenance phase for a period of 24 weeks.
Expected outcomes and significance: If this method proves to be equivalent to EEN, the duration of use of EEN will be only two weeks, allowing more patients access to dietary therapy. More importantly, this study will also evaluate two maintenance strategies and will be the first to evaluate re-biosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Crohn's Disease, Pediatric, Exclusive Enteral Nutrition, Diet, Microbiome
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Modified Exclusive Enteral Nutrition including two weeks of Exclusive Enteral Nutrition (EEN) using Modulen followed by Partial Enteral Nutrition (PEN) along with the Crohn's Disease Exclusion Diet (CDED) phases 2 & 3 for 24 weeks
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
Standard Exclusive Enteral Nutrition for 8 weeks using Modulen, followed by free diet with gradual reduction of Modulen to 25% of energy needs by week 24.
Intervention Type
Other
Intervention Name(s)
Modified Exclusive Enteral Nutrition
Other Intervention Name(s)
Modulen, Nestle
Intervention Description
Two weeks of Exclusive Enteral Nutrition with Modulen
Intervention Type
Other
Intervention Name(s)
Crohn's Disease Exclusion Diet
Other Intervention Name(s)
CDED
Intervention Description
a limited whole food diet
Intervention Type
Other
Intervention Name(s)
Partial Enteral Nutrition
Other Intervention Name(s)
Modulen, Nestle
Intervention Description
25-50% of Energy from formula
Intervention Type
Other
Intervention Name(s)
Standard Exclusive Enteral Nutrition
Other Intervention Name(s)
Modulen, Nestle
Intervention Description
8 weeks of Exclusive Enteral Nutrition
Primary Outcome Measure Information:
Title
ITT, steroid free Clinical remission (defined as Pediatric Crohn's Disease Activity Index (PCDAI)<10) at week 14
Description
Sustained remission with EEN Vs CDED+PEN
Time Frame
week 14
Secondary Outcome Measure Information:
Title
ITT steroid free remission at week 8
Description
Induction of remission
Time Frame
week 8
Title
Microbiome composition difference between groups at week 14
Description
Assessment of microbiome composition and metabolomics
Time Frame
week 14
Title
3. Reduction of at least 50% from baseline in fecal calprotectin at week 24 for patients on original treatment
Description
Mucosal healing assessment
Time Frame
week 24
Title
Steroid and biologic free sustained remission at week 24.
Description
Remission achieved and maintained without additional therapy
Time Frame
week 14 and 24
Title
Need for additional treatment to achieve remission by week 14
Description
Remission achieved without additional therapy
Time Frame
Week 14
Title
Mucosal healing as assessed by MRE in dietary responsive disease at week 52
Description
Mucosal healing
Time Frame
Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Established diagnosis of Crohn's disease.
Patients with mild to severe active Crohn's disease (15≤PCDAI≤47.5)
Ages 8-18
Duration of disease ≤ 36 months
Active inflammation (CRP≥>0.6 mg /dL or ESR≥>20 or Calprotectin≥>200 mcg/gr within the past 3 weeks) during screening
Patients with B1, P0 uncomplicated disease at enrollment
Patients with disease defined as L1, L4, L3 or L2 limited to cecum, ascending or transverse colon or L2 with left sided disease with terminal ileum or small bowel involvement in the past by the Paris classification (patients with macroscopic disease)
Signed informed consent
Exclusion Criteria:
Patients with very mild disease (PCDAI 12.5 -15) or very severe disease (PCDAI >47.5)
Pregnancy
Patients who have disease confined to the colon involving the descending colon, rectum or sigmoid colon and no prior history of small bowel involvement
Patients who have active extra intestinal disease (such as Arthritis, Uveitis, Pyoderma Gangrenosum, Erythema Nodosum etc.)
Patients with complicated disease (B2, B3)
Patients who recently onset use of an immunomodulator <8 weeks, or dose change in past 8 weeks.
Patients with current use of biologics, or use in last 8 weeks or current use of systemic steroids
Patients who have active perianal disease ( active fistula or abscess)
Patients who have positive stool cultures with relevant pathogens,, or positive tests for parasites or C. difficile. Stool tests are mandatory only if diarrhea is present.
Patients with fever > 38.3
Documented milk protein allergy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rotem Sigall Boneh, RD
Organizational Affiliation
Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michal Yaakov
Organizational Affiliation
Pediatric Gastroenterology and Nutrition unit; The E. Wolfson.Medical Center
Official's Role
Study Director
Facility Information:
Facility Name
Dr. Eytan Wine,
City
Edmonton
Country
Canada
Facility Name
Johan Van Limbergen
City
Halifax
Country
Canada
Facility Name
Dr Sally Lawrence
City
Vancouver
Country
Canada
Facility Name
Dr. Séamus Hussey
City
Dublin
Country
Ireland
Facility Name
The E. Wolfson.Medical Center
City
Holon
ZIP/Postal Code
58100
Country
Israel
Facility Name
Dr. Francisco Javier Martin Carpi
City
Barcelona
Country
Spain
Facility Name
Dr. Víctor Manuel Navas López
City
Málaga
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24983973
Citation
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.
Results Reference
background
PubMed Identifier
31170412
Citation
Levine A, Wine E, Assa A, Sigall Boneh R, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J. Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021. Epub 2019 Jun 4.
Results Reference
background
PubMed Identifier
28525622
Citation
Sigall Boneh R, Sarbagili Shabat C, Yanai H, Chermesh I, Ben Avraham S, Boaz M, Levine A. Dietary Therapy With the Crohn's Disease Exclusion Diet is a Successful Strategy for Induction of Remission in Children and Adults Failing Biological Therapy. J Crohns Colitis. 2017 Oct 1;11(10):1205-1212. doi: 10.1093/ecco-jcc/jjx071.
Results Reference
background
Learn more about this trial
Diet for Induction and Maintenance of Remission and Re-biosis in Crohn's Disease
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