Clinical trial NCT05951153: Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation
Official title: Phase I, Single-arm, Dose-escalation Trial of Tributyrin to Promote Gut Health Among Children Undergoing Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hematopoietic Cell Transplantation (HCT)
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2023-07-18
Enrollment: 0
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of tributyrin among children undergoing hematopoietic cell transplantation (HCT)
timeFrame: 36 months
Secondary outcomes:
measure: Change in fecal butyrate concentration
timeFrame: Baseline, 36 months
measure: Change in gut microbiome composition
timeFrame: Baseline, 36 months
measure: Change in gut inflammation
timeFrame: Baseline, 36 months
measure: Change in gut barrier integrity
timeFrame: Baseline, 36 months
Other outcomes:
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