PRecisiOn Microbiome Directed ExtensiOn of Anti-TNFα Crohn's Disease ThErapy in Children: The PROMOTE Trial (PROMOTE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease
• Intervention / Treatment: Other: Placebo; Other: Resistant Starch

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
      • Contact: David Mack, MD, FRCPC; Phone Number: 2516 (613)737-7600; Email: dmack@cheo.on.ca
      • Contact: Ruth Singleton, RN, CCRP; Phone Number: 4123 (613)737-7600; Email: rsingleton@cheo.on.ca
      • Principal Investigator: David Mack, MD, FRCPC
      • Principal Investigator: Alain Stintzi, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Other: Resistant Starch; 7.5g/m2 or 5.0g/m2 (body surface area) resistant starch oral consumption
Placebo Comparator: 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	Other: Placebo; Placebo oral consumption of food-grade cornstarch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of butyrate production by assessing expression of enzymes using metaproteomic/transcriptomic analysis	Measures of restoration and sustainment of butyrate production by using metaproteomic/transcription to assess the expression of enzymes invovled in butyrate production	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
Measure of butyrate production by assessing production of shorty-chain-fatty-acids including butyrates using metabolomics analysis	Measures of restoration and sustainment of butyrate production by using metabolomics analysis to assess production of short-chain-fatty acids including butyrate.	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
Measure of butyrate production by assessing increases in butyrate producers using metagenomics/16S analysis	Measures of restoration and sustainment of butyrate production by metagenomics/16s analysis to assess increases in butyrate producers	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in intensification as measured by anti-TNFa dose escalation	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	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Change in intensification as measured by anti-TNFa interval shortening	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	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Change in disease activity	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).	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Changes in intestinal mucosal inflammation by measuring fecal calprotectin through stool samples	Measure of fecal calprotectin	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
Changes in biomarkers of inflammation by measuring c-reactive protein through blood samples	Measure of c-reactive protein	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks
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.	Baseline, 24 weeks, 48 weeks
Changes in patient reported quality of life outcomes as measured by the IMPACT III Questionnaire	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.	Baseline, 24 weeks, 48 weeks
Changes in parent/caregiver reported quality of life outcomes as measured by the IMPACT III-P	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.	Baseline, 24 weeks, 48 weeks

Collaborators and Investigators

• Sponsor: Children's Hospital of Eastern Ontario

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 2, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Microbiome; Resistant Starch; anti-TNF
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 23/109X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No