Clinical trial NCT04522271: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Crohn Disease
Ulcerative Colitis
Inflammatory Bowel Diseases
Keywords: Resistant Starch
Microbiome
Lead sponsor: Children's Hospital of Eastern Ontario
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 80
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single center, randomized, placebo-controlled, double-blinded, parallel, pilot clinical trial
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: 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.
timeFrame: 5 ± 1 months
measure: 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.
timeFrame: 12 ± 2 months
measure: The percentage of eligible inflammatory bowel disease (IBD) patients who will enter a resistant starch-based ingestion trial.
timeFrame: Enrollment
measure: Compliance of resistant starch intake by patient report.
timeFrame: 5 ± 1 months
measure: Compliance of resistant starch intake by product reconciliation.
timeFrame: 5 ± 1 months
Secondary outcomes:
measure: Change in microbiome composition of cases towards the microbiome of controls as assessed by meta-omics analysis.
timeFrame: 5 ± 1 months and 12 ± 2 months
measure: Changes in mitochondrial function due to ingestion of resistant starch as assessed by host proteomics of biopsy sampling.
timeFrame: Enrollment, and 5 ± 1 months
measure: 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.
timeFrame: Enrollment, 5 ± 1 months, and 12 ± 2 months
measure: Changes in patient reported disability outcomes as measured by the IBD Disability Index Questionnaire.
timeFrame: Enrollment, 5 ± 1 months, and 12 ± 2 months
measure: Changes in patient, parent/caregiver reported quality of life outcomes as measured by the IMPACT III Questionnaires.
timeFrame: Enrollment, 5 ± 1 months, and 12 ± 2 months
measure: Changes in intestinal mucosal inflammation by measuring fecal calprotectin through stool samples.
timeFrame: Enrollment, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 8 months, 10 months, and 12 months
measure: 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.
timeFrame: Enrollment, and 5 ± 1 months
measure: 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.
timeFrame: Enrollment, and 5 ± 1 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Hospital of Eastern Ontario
name: David Mack, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ottawa
name: Alain Stintzi, PhD
role: PRINCIPAL_INVESTIGATOR
References: