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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Hematopoietic Cell Transplantation (HCT)
• Intervention / Treatment: Combination product: Tributyrin

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sarah M Heston, MD; Phone Number: 919-684-6335; Email: sarah.heston@duke.edu
• Study Contact Backup: Name: Matthew S Kelly, MD; Phone Number: 919-668-4855; Email: matthew.kelly@duke.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 2-17 years with standard of care nasogastric tube placement or existing gastric tubes
• Planned allogeneic hematopoietic cell transplantation with myeloablative preparative regimen
• Planned graft-versus-host-disease prophylaxis with calcineurin inhibitor + mycophenoalte mofetil or calcineurin inhibitor + methotrexate

Exclusion Criteria:

• Previous history of hematopoietic cell transplantataion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tributyrin nutritional supplement; Children between the ages of 2-17 with planned allogeneic hematopoietic cell transplantation with myeloablative preparative regimen, who also have standard of care nasogastric tube placement or existing gastric tubes will receive a daily dose of tributyrin.	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.; Other Names: Nutritional supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) of tributyrin among children undergoing hematopoietic cell transplantation (HCT)	An evaluation of the safety and tolerability of tributyrin.	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in fecal butyrate concentration	Baseline, 36 months
Change in gut microbiome composition	Baseline, 36 months
Change in gut inflammation	Baseline, 36 months
Change in gut barrier integrity	Baseline, 36 months

Collaborators and Investigators

• Sponsor: Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: June 26, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: Pro00112603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD sharing plan is undecided by study team at this time.

Drug and device information, study documents

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