Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation

Early Phase 1

Withdrawn

• Conditions: Hematopoietic Cell Transplantation (HCT)
• Interventions: Combination Product: Tributyrin

• Registration Number: NCT05951153
• Lead Sponsor: Duke University

Brief 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.

Study Timeline

• Study First Submitted: 2023-06-26
• Study First Submitted QC: 2023-07-11
• Study First Posted: 2023-07-18
• Status Verified: 2024-08
• Study Start: 2024-08-01
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-15
• Primary Completion: 2025-11
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tributyrin nutritional supplement	Tributyrin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in gut microbiome composition	Baseline, 36 months
Change in fecal butyrate concentration	Baseline, 36 months
Change in gut inflammation	Baseline, 36 months
Change in gut barrier integrity	Baseline, 36 months