PRecisiOn Microbiome Directed ExtensiOn of Anti-TNFα Crohn's Disease ThErapy in Children: the PROMOTE Trial
- Conditions
- Crohn DiseaseInflammatory Bowel Diseases
- Interventions
- Other: Resistant StarchOther: Placebo
- Registration Number
- NCT06301477
- Lead Sponsor
- Children's Hospital of Eastern Ontario
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 45
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Resistant Starch Resistant Starch Once daily oral consumption of either 7.5g/m2 or 5.0g/m2 (body surface area) of a resistant starch for 48 weeks that is individually optimized at 24 weeks. Placebo Placebo Once daily oral consumption of a readily digestible food-grade cornstarch that resembles the study product in appearance, smell and taste for 48 weeks
- Primary Outcome Measures
Name Time Method 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 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 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 Outcome Measures
Name Time Method 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).
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
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 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 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.
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
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 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
Trial Locations
- Locations (1)
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada