Back to resultsResistant Starch in Pediatric Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)
Primary Purpose
Crohn Disease, Ulcerative Colitis, Inflammatory Bowel Diseases
Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Resistant Starch
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Crohn Disease focused on measuring Resistant Starch, Microbiome
Eligibility Criteria
Inclusion Criteria:
- Capable of giving informed consent, or if appropriate, have an acceptable representative capable of giving consent on the participant's behalf.
- Enrolled in the main parent study.
- New ulcerative colitis diagnosis (mild/moderate) or Crohn's Disease diagnosis (moderate/severe) with colonic disease with or without terminal ileum disease, already started on oral corticosteroid or aminosalicylates for induction therapy at a time following diagnostic colonoscopy.
- Clinically responsive to induction medical therapy at enrollment (Crohn's Disease participants with a weighted pediatric Crohn's Disease activity index decrease of ≥ 17.5 points or ulcerative colitis participants with a pediatric ulcerative colitis activity index decrease of ≥ 15 points).
- Ability and willingness to comply with study procedures (e.g. stool collections) for the entire length of the study.
- Willing to provide consent/assent for the collection of stool samples.
Exclusion Criteria:
- Allergy to resistant starch or excipients.
- Co-existing diagnosis with diabetes mellitus.
- Treatment with another investigational drug or intervention throughout the study.
- Current drug or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of an individual or legal guardian to give written informed consent.
- Requirement for antibiotic therapy as part of standard Crohn's Disease therapy (i.e. those patients with penetrating disease as manifested by intra-abdominal abscess or perianal abscess).
- Requirement of oral antibiotics for other conditions (e.g. acne).
- Participant's microbiota does not produce butyrate in response to any of the assembled panel of resistant starch as measured through the Rapid Assay of an Individual's Microbiome (RapidAIM) evaluation following enrollment.
- Requirement of therapy other than oral corticosteroid / aminosalicylates for induction therapy.
- Patients diagnosed with Inflammatory Bowel Disease-Unclassified.
- Refusal to undergo follow-up colonoscopy as part of current clinical practice guidelines for Crohn's Disease standard of care.
Sites / Locations
- Children's Hospital of Eastern Ontario
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Resistant Starch
Placebo
Arm Description
Once daily oral consumption of 7.5 g/m2 of an individually optimized resistant starch for approximately 5 months
Once daily oral consumption of a food-grade cornstarch that is readily digestible for approximately 5 months
Outcomes
Primary Outcome Measures
Increased potential for butyrate production and its level at the mucosal luminal interface following ingestion of an individualized resistant starch as assessed by meta-omics analysis.
Sustained increased potential of butyrate production 6 months following cessation of the use of individualized resistant starch as assessed by meta-omics analysis of stools.
The percentage of eligible inflammatory bowel disease (IBD) patients who will enter a resistant starch-based ingestion trial.
Threshold of interest will be 50%.
Compliance of resistant starch intake by patient report.
Compliance of resistant starch intake by product reconciliation.
Secondary Outcome Measures
Change in microbiome composition of cases towards the microbiome of controls as assessed by meta-omics analysis.
Changes in mitochondrial function due to ingestion of resistant starch as assessed by host proteomics of biopsy sampling.
Change in clinical disease activity as measured by the wPCDAI for Crohn's Disease, the PUCAI and Partial Mayo Score for Ulcerative Colitis, and the PGA for both Crohn's Disease and Ulcerative Colitis.
Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) ranges from 0 to 125 points (<12.5 = remission, 12.5 to 40.0 = mild, >40.0 = moderate, >57.5 = severe). The Pediatric Ulcerative Colitis Activity Index (PUCAI) ranges from 0 to 85 points (<10 = remission, 10 to 34 = mild, 35 to 64= moderate, >65 = severe). Partial Mayo Score ranges from 0 to 9 points (0 to 1 = remission, 2 to 4 = mild, 5 to 6 = moderate, 7 to 9 = severe). The Physician Global Assessment (PGA) ranges from 0 to 3 points (0 = normal, 1 = mild, 2 = moderate, 3 = severe).
Changes in patient reported disability outcomes as measured by the IBD Disability Index Questionnaire.
The IBD disability index consists of 28 questions and a higher overall score is indicative of greater disability.
Changes in patient, parent/caregiver reported quality of life outcomes as measured by the IMPACT III Questionnaires.
The IMPACT III questionnaire (a health related quality of life questionnaire) consists of 35 questions and ranges in score from 0 to 231. A higher score represents a higher quality of life. The IMPACT III-P Questionnaire is to be completed by the caregiver/guardian with a higher score also representing a higher quality of life.
Changes in intestinal mucosal inflammation by measuring fecal calprotectin through stool samples.
Change in endoscopic disease activity measured during colonoscopies using the SES-CD for Crohn's Disease and the Mayo Endoscopic Sub Score and UCEIS for Ulcerative Colitis.
The Simple Endoscopic Score for Crohn's Disease (SES-CD) measures disease inflammation (0 to 2= inactive, 3 to 6 = mild, 7 to 15 = moderate, >16 = severe). Mayo Endoscopic Sub Scores range from 0 to 3, with 0 representing a normal mucosa or inactive disease and 3 representing severe activity (spontaneous bleeding and large ulcerations). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ranges from 0 to 8 (0 to 1 = remission, 2 to 4 = mild, 5 to 6 = moderate, and 7 to 8 = severe).
Change in histological scoring of acute and chronic inflammation collected through biopsies during colonoscopies and assessed using Naini and Cortina score for Crohn's disease and the Robarts Histopathological Index (RHI) for Ulcerative Colitis.
The Naini and Cortina score ranges from 0 to 10 for ileitis and 0 to 17 for colitis. For ileitis, the histopathological support for having IBD is either low (score < 2), moderate (score is 3 to 4), or high (score ≥ 5). For colitis, the likelihood of having IBD is either low (≤3), moderate (score is 4 to 8), or high (score ≥ 9). The Robarts Histopathological Index score ranges from 0 to 33 with a higher score representing more severe inflammation.
Full Information
NCT ID
NCT04522271
First Posted
July 31, 2020
Last Updated
May 26, 2023
Sponsor
Children's Hospital of Eastern Ontario
1. Study Identification
Unique Protocol Identification Number
NCT04522271
Brief Title
Resistant Starch in Pediatric Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)
Official Title
A Single Center, Randomized, Placebo-controlled, Double-blinded, Parallel, Pilot Clinical Trial to Assess Plant-derived Food-based Resistant Starches Individually Optimized for Patients With Crohn's Disease (CD) or Ulcerative Colitis (UC)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 25, 2020 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Eastern Ontario
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 purpose of the study is determine if a plant-based resistant starch that is optimized for the individual will target the underlying cause of inflammatory bowel disease and restore a "healthier" gut microbiome in pediatric participants with inflammatory bowel disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease, Ulcerative Colitis, Inflammatory Bowel Diseases
Keywords
Resistant Starch, Microbiome
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
A single center, randomized, placebo-controlled, double-blinded, parallel, pilot clinical trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Unblinding will occur only if necessary to ensure study participants safety, interim analysis at 5 ± 1 months, or eligibility for our associated open label trial (OARS trial). Only Dr. Mack (Co-PI) can request to break the blind for safety reasons or eligibility for the OARS Trial; only Dr Stintzi (Co-PI) will request to break the blind for interim analysis. Once the blind is broken, the patient will be discontinued from study product.
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Resistant Starch
Arm Type
Active Comparator
Arm Description
Once daily oral consumption of 7.5 g/m2 of an individually optimized resistant starch for approximately 5 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Once daily oral consumption of a food-grade cornstarch that is readily digestible for approximately 5 months
Intervention Type
Other
Intervention Name(s)
Resistant Starch
Intervention Description
7.5 g resistant starch/m2 oral consumption
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo oral consumption of food-grade cornstarch
Primary Outcome Measure Information:
Title
Increased potential for butyrate production and its level at the mucosal luminal interface following ingestion of an individualized resistant starch as assessed by meta-omics analysis.
Time Frame
5 ± 1 months
Title
Sustained increased potential of butyrate production 6 months following cessation of the use of individualized resistant starch as assessed by meta-omics analysis of stools.
Time Frame
12 ± 2 months
Title
The percentage of eligible inflammatory bowel disease (IBD) patients who will enter a resistant starch-based ingestion trial.
Description
Threshold of interest will be 50%.
Time Frame
Enrollment
Title
Compliance of resistant starch intake by patient report.
Time Frame
5 ± 1 months
Title
Compliance of resistant starch intake by product reconciliation.
Time Frame
5 ± 1 months
Secondary Outcome Measure Information:
Title
Change in microbiome composition of cases towards the microbiome of controls as assessed by meta-omics analysis.
Time Frame
5 ± 1 months and 12 ± 2 months
Title
Changes in mitochondrial function due to ingestion of resistant starch as assessed by host proteomics of biopsy sampling.
Time Frame
Enrollment, and 5 ± 1 months
Title
Change in clinical disease activity as measured by the wPCDAI for Crohn's Disease, the PUCAI and Partial Mayo Score for Ulcerative Colitis, and the PGA for both Crohn's Disease and Ulcerative Colitis.
Description
Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) ranges from 0 to 125 points (<12.5 = remission, 12.5 to 40.0 = mild, >40.0 = moderate, >57.5 = severe). The Pediatric Ulcerative Colitis Activity Index (PUCAI) ranges from 0 to 85 points (<10 = remission, 10 to 34 = mild, 35 to 64= moderate, >65 = severe). Partial Mayo Score ranges from 0 to 9 points (0 to 1 = remission, 2 to 4 = mild, 5 to 6 = moderate, 7 to 9 = severe). The Physician Global Assessment (PGA) ranges from 0 to 3 points (0 = normal, 1 = mild, 2 = moderate, 3 = severe).
Time Frame
Enrollment, 5 ± 1 months, and 12 ± 2 months
Title
Changes in patient reported disability outcomes as measured by the IBD Disability Index Questionnaire.
Description
The IBD disability index consists of 28 questions and a higher overall score is indicative of greater disability.
Time Frame
Enrollment, 5 ± 1 months, and 12 ± 2 months
Title
Changes in patient, parent/caregiver reported quality of life outcomes as measured by the IMPACT III Questionnaires.
Description
The IMPACT III questionnaire (a health related quality of life questionnaire) consists of 35 questions and ranges in score from 0 to 231. A higher score represents a higher quality of life. The IMPACT III-P Questionnaire is to be completed by the caregiver/guardian with a higher score also representing a higher quality of life.
Time Frame
Enrollment, 5 ± 1 months, and 12 ± 2 months
Title
Changes in intestinal mucosal inflammation by measuring fecal calprotectin through stool samples.
Time Frame
Enrollment, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 8 months, 10 months, and 12 months
Title
Change in endoscopic disease activity measured during colonoscopies using the SES-CD for Crohn's Disease and the Mayo Endoscopic Sub Score and UCEIS for Ulcerative Colitis.
Description
The Simple Endoscopic Score for Crohn's Disease (SES-CD) measures disease inflammation (0 to 2= inactive, 3 to 6 = mild, 7 to 15 = moderate, >16 = severe). Mayo Endoscopic Sub Scores range from 0 to 3, with 0 representing a normal mucosa or inactive disease and 3 representing severe activity (spontaneous bleeding and large ulcerations). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ranges from 0 to 8 (0 to 1 = remission, 2 to 4 = mild, 5 to 6 = moderate, and 7 to 8 = severe).
Time Frame
Enrollment, and 5 ± 1 months
Title
Change in histological scoring of acute and chronic inflammation collected through biopsies during colonoscopies and assessed using Naini and Cortina score for Crohn's disease and the Robarts Histopathological Index (RHI) for Ulcerative Colitis.
Description
The Naini and Cortina score ranges from 0 to 10 for ileitis and 0 to 17 for colitis. For ileitis, the histopathological support for having IBD is either low (score < 2), moderate (score is 3 to 4), or high (score ≥ 5). For colitis, the likelihood of having IBD is either low (≤3), moderate (score is 4 to 8), or high (score ≥ 9). The Robarts Histopathological Index score ranges from 0 to 33 with a higher score representing more severe inflammation.
Time Frame
Enrollment, and 5 ± 1 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Capable of giving informed consent, or if appropriate, have an acceptable representative capable of giving consent on the participant's behalf.
Enrolled in the main parent study.
New ulcerative colitis diagnosis (mild/moderate) or Crohn's Disease diagnosis (moderate/severe) with colonic disease with or without terminal ileum disease, already started on oral corticosteroid or aminosalicylates for induction therapy at a time following diagnostic colonoscopy.
Clinically responsive to induction medical therapy at enrollment (Crohn's Disease participants with a weighted pediatric Crohn's Disease activity index decrease of ≥ 17.5 points or ulcerative colitis participants with a pediatric ulcerative colitis activity index decrease of ≥ 15 points).
Ability and willingness to comply with study procedures (e.g. stool collections) for the entire length of the study.
Willing to provide consent/assent for the collection of stool samples.
Exclusion Criteria:
Allergy to resistant starch or excipients.
Co-existing diagnosis with diabetes mellitus.
Treatment with another investigational drug or intervention throughout the study.
Current drug or alcohol dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Inability or unwillingness of an individual or legal guardian to give written informed consent.
Requirement for antibiotic therapy as part of standard Crohn's Disease therapy (i.e. those patients with penetrating disease as manifested by intra-abdominal abscess or perianal abscess).
Requirement of oral antibiotics for other conditions (e.g. acne).
Participant's microbiota does not produce butyrate in response to any of the assembled panel of resistant starch as measured through the Rapid Assay of an Individual's Microbiome (RapidAIM) evaluation following enrollment.
Requirement of therapy other than oral corticosteroid / aminosalicylates for induction therapy.
Patients diagnosed with Inflammatory Bowel Disease-Unclassified.
Refusal to undergo follow-up colonoscopy as part of current clinical practice guidelines for Crohn's Disease standard of care.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Mack, MD, FRCPC
Organizational Affiliation
Children's Hospital of Eastern Ontario
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alain Stintzi, PhD
Organizational Affiliation
University of Ottawa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Resistant Starch in Pediatric Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)
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