Pancreatic Enzymes and Bile Acids: A Non-Antibiotic Approach to Treat Intestinal Dysbiosis in Acutely Ill Severely Malnourished Children (CHAIN 2.0/PB-SAM)
Information:
Sponsor - Bill and Melinda Gates Foundation
Principal Investigators – Robert Bandsma, Wieger Voskuijl, and James Berkley, University of Oxford; Ezekiel Mupere, MBChB, MMed, PhD, Uganda-CWRU Research Collaboration; Christina Lancioni, MD, Oregon Health & Science University; Johnstone Thitiri, KEMRI/Kenya, Caroline Ogwang, KEMRI/Kenya; Emmie Mbale, Malawi; Mohammod Jobayer, Bangladesh, Robert Bandsma, Canada
| Type of Study | Multi-center clinical treatment trial |
|---|---|
| Design | Randomized, double-blind, controlled clinical trial |
| Project Site | Kampala, Uganda (additional performance sites include Kenya, Malawi and Bangladesh) |
| Sample Size | 200 participants at all sites; subsequent 3 stages following interim analyses may increase sample size to 400, 800 and 1200 participants |
| Study Period |
2021 - 2023 Enrollment/treatment period is 60 days |
Goal of Study:
This trial aims to test if administration of bile acid and/or pancreatic enzyme supplementation, in addition to standard-of-care interventions including empiric antibiotics, improves clinical outcomes in sick, malnourished children. This approach addresses specific mechanisms that have been identified in severely malnourished children and could impact intestinal function and the local and systemic effects of bacterial dysbiosis. This in turn can reduce bacterial translocation across the intestinal lumen and systemic inflammation or bacteremia.
Primary Objective:
To determine whether treatment with pancreatic enzymes or bile acids reduce mortality in acutely ill hospitalized children with severe malnutrition compared to placebo.
To determine -
- Rate and type of safety adverse events (SAEs, including readmissions to hospital)
- Safety: rate of grade 3 or 4 toxicity events whilst receiving investigational products
- Intestinal function: number of days with diarrhea during admission
- Use of second and third-line antibiotics during admission and readmission
- Number of days from enrollment to discharge during admission
- Growth: (MUAC, weight-for-length, length-for-age) to day 60.