Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation

NCT ID: NCT05951153

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2026-11-30

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.

Conditions

Hematopoietic Cell Transplantation (HCT)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tributyrin

Intervention Type: COMBINATION_PRODUCT

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.

Interventions

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.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Nutritional supplement

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

Pro00112603

Identifier Type: -

Identifier Source: org_study_id