Crohn Disease, Inflammatory Bowel Diseases
Conditions
Keywords
Resistant Starch, Microbiome, anti-TNF
Brief summary
To determine whether a specific food-origin plant-derived resistant starch (RS) optimized for the individual will increase the abundance of known butyrate producing microbes.
Interventions
OTHERResistant Starch
7.5g/m2 or 5.0g/m2 (body surface area) resistant starch oral consumption
OTHERPlacebo
Placebo oral consumption of food-grade cornstarch
Sponsors
Children's Hospital of Eastern Ontario
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The treating physician, study participants, and research coordinators and lab researchers will not have knowledge of the randomization codes and will be blinded as to study product allocation. Unblinding will occur only if necessary to ensure study participants safety. Only Dr. Mack (Co-PI) will request to break the blind for safety reasons. Once the blind is broken by Dr. Mack the patient will be discontinued from study product.
Intervention model description
A single-center, randomized, placebo-controlled, double-blinded, pilot trial
Eligibility
Sex/Gender
ALL
Age
8 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Age between 8.0 to 16.9 years of age. * Capable of giving informed consent, or if appropriate, have an acceptable representative capable of giving consent on the participant's behalf. * Established Crohn's Disease (CD) diagnosis with the site of disease involving at least the terminal ileum or ascending colon. * CD is in clinical remission or with mild stable disease activity (weighted Pediatric Crohn's Disease Activity Index of 0 to 39.5). * Receiving infliximab or adalimumab anti-TNFa monoclonal antibody medication for treatment of CD. * No changes in medical treatment for the previous month and without anticipated changes for the next month. * Ability and willingness to comply with study procedures (e.g., stool collection) for the entire length of the study.
Exclusion criteria
* Allergy to RS or excipients. * Co-existing diagnosis with diabetes mellitus type 1. * Treatment with another investigational drug or intervention throughout the study. * Current illicit drug or alcohol dependence. * Inability or unwillingness of an individual or legal guardian to give written informed consent. * Other conditions requiring immunomodulating or biological medications. * Pregnancy. * Participant's microbiota does not increase butyrate production utilizing any RS from the assembled panel as measured through the RapidAIM ex vivo assay.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of butyrate production by assessing expression of enzymes using metaproteomic/transcriptomic analysis | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks. | Measures of restoration and sustainment of butyrate production by using metaproteomic/transcription to assess the expression of enzymes invovled in butyrate production |
| Measure of butyrate production by assessing production of shorty-chain-fatty-acids including butyrates using metabolomics analysis | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks. | Measures of restoration and sustainment of butyrate production by using metabolomics analysis to assess production of short-chain-fatty acids including butyrate. |
| Measure of butyrate production by assessing increases in butyrate producers using metagenomics/16S analysis | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks. | Measures of restoration and sustainment of butyrate production by metagenomics/16s analysis to assess increases in butyrate producers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in intensification as measured by anti-TNFa dose escalation | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks | To help contextualize the anti-TNFa dose escalation (if applicable), Infliximab or adalimumab information will be recorded at baseline, 12 weeks, 24 weeks, 36 weeks and 48 weeks after start of study product. Type of anti-TNFa drug prescribed, amount of anti-TNFa prescribed, dose changes in timing of administration, trough drug serum levels, weight changes and reason for dose changes will be recorded |
| Change in intensification as measured by anti-TNFa interval shortening | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks | To help contextualize the anti-TNFa interval shortening (if applicable), Infliximab or adalimumab information will be recorded at baseline, 12 weeks, 24 weeks, 36 weeks and 48 weeks after start of study product. Type of anti-TNFa drug prescribed, amount of anti-TNFa prescribed, dose changes in timing of administration, trough drug serum levels, weight changes and reason for dose changes will be recorded |
| Change in disease activity | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks | 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). |
| Changes in intestinal mucosal inflammation by measuring fecal calprotectin through stool samples | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks | Measure of fecal calprotectin |
| Changes in biomarkers of inflammation by measuring c-reactive protein through blood samples | Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks | Measure of c-reactive protein |
| Changes in patient reported disability outcomes as measured by the IBD Disability Index Questionnaire | Baseline, 24 weeks, 48 weeks | The IBD Disability Index consists of 28 questions and a higher overall score is indicative of greater disability. |
| Changes in patient reported quality of life outcomes as measured by the IMPACT III Questionnaire | Baseline, 24 weeks, 48 weeks | 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. |
| Changes in parent/caregiver reported quality of life outcomes as measured by the IMPACT III-P | Baseline, 24 weeks, 48 weeks | The IMPACT III-P 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. |
Countries
Canada
Outcome results
None listed