NCT05951153

Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation

Phase I, Single-arm, Dose-escalation Trial of Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Duke University · Academic / Other
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

To determine the safety and tolerability of tributyrin among children undergoing hematopoietic cell transplantation (HCT).

Detailed description

Primary Objectives: 1\. Evaluate the safety and tolerability of tributyrin and determine the maximum tolerated dose MTD among children undergoing hematopoietic cell transplantation (HCT). Secondary Objectives: 1. Determine the effect of tributyrin administration on fecal butyrate concentrations. 2. Measure the effect of tributyrin on gut microbiome composition and measures of gut inflammation and barrier integrity. Hypotheses 1. Enteral administration of tributyrin will be safe and well-tolerated in children undergoing HCT at doses up to 100 mg/kg/day, with no identified dose-limiting toxicities. The most common adverse events will be gastrointestinal and will occur at frequencies and grades typically observed among children after HCT. No adverse effects will occur that are classified as probably or definitely related to the study product. 2. Tributyrin will result in a dose-dependent increase in fecal butyrate concentrations, with maximal fecal butyrate concentrations exceeding concentrations in baseline fecal samples by at least two-fold in \>50% of subjects at all evaluated tributyrin doses. 3. Compared to historical controls, children receiving tributyrin will have greater preservation of gut microbial diversity and higher abundances of Clostridiales and other putatively beneficial gut anaerobes (e.g., Bifidobacterium, Lactobacillus) after HCT. Additionally, children receiving tributyrin will have lower fecal levels of calprotectin and lactoferrin and lower plasma levels of lipopolysaccharide-binding protein and intestinal fatty acid-binding protein, corresponding to lower levels of intestinal inflammation and improved gut barrier function.

Conditions

• Hematopoietic Cell Transplantation (HCT)

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Tributyrin	Tributyrin is a nutritional supplement prepared by esterification of glycerin with butyric acid that promotes delivery of free butyrate to distal portions of the gut.

Timeline

• Start date: 2024-08-01
• Primary completion: 2025-11-01
• Completion: 2026-11-01
• First posted: 2023-07-18
• Last updated: 2024-08-15

Regulatory

• FDA-regulated drug study