Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation

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

Detailed Description
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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: Determine the effect of tributyrin administration on fecal butyrate concentrations. Measure the effect of tributyrin on gut microbiome composition and measures of gut inflammation and barrier integrity. Hypotheses 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. 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. 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.

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

Conditions
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Hematopoietic Cell Transplantation (HCT)

Intervention / Treatment
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* Combination Product: Tributyrin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tributyrin nutritional supplement<br>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<br>* 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.<br>* Other names: Nutritional supplement;|

What is the study measuring?
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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 | Measure Description | 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 |