Clinical trial NCT06882772: Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids
Official title: Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids, A Phase IIa Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Congenital Heart Disease (CHD)
Keywords: Congenital Heart Disease
Gut Health
Microbiome
Gut Barrier Function
Inflammation
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2025-03-19
Enrollment: 105
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Butyric acid has been shown to promote gut health and improve the microbiome in multiple adult studies. In preliminary studies in older children with inflammatory bowel disease, butyric acid was shown to be safe. However, it's suitability for infants and young children with congenital heart disease (CHD) has yet to be determined.

This study will examine butyric acid supplementation in infants and children, ages 1 month to 3 years, with CHD who require cardiac surgery with cardiopulmonary bypass. Study goals include determining the safety and tolerability of butyric acid supplementation before cardiac surgery, and to identify changes in gut microbial communities, metabolic profile, and genetic markers intestinal function. Also, the study seeks to establish a reduction in inflammation (inflammatory signaling) after cardiopulmonary bypass (CPB) in participants receiving butyric acid.

Detailed description: The goal of this study is to supplement a liquid form of butyric acid once daily for 3 weeks prior to cardiac surgery for infants and children, ages 1 month to 3 years, with congenital heart disease to improve their pre-operative gut microbiome in efforts to reduce post-operative gut permeability and reduce post-operative inflammatory signaling.

Up to 35 participants will be enrolled in each of three arms:

* 2 mL butyric acid
* 4 mL butyric acid
* Placebo.

Participants will be asked to:

* Provide blood and stool samples (baseline, post-supplement-pre-operative, 1-hr post-op, \& post-op days 1-3)
* Take either 2 mL, 4 mL or placebo once daily for 3 weeks prior to cardiac surgery
* Complete a daily log to track timing of supplement administration and any side effects or adverse events experienced

Study aims:

* Aim 1 Safety and tolerability will be measured following baseline complete blood counts, complete metabolic panel to evaluate electrolytes and organ function, along with a daily log of supplementation timing and any experienced adverse events.
* Aim 2 Modulation of gut health will be measured with stool and blood samples. Changes will be measured in the gut microbiome and metabolite profiles before and after supplementation, as well as post-operatively. Gut health will be determined by measuring plasma markers of gut barrier function before and after supplementation, as well as post-operatively.
* Aim 3 Reduction of post-operative inflammatory signaling will be measured with blood samples. Plasma cytokine levels, immune cell profiles, and inflammatory gene activation with an RNA hybridization panel will be measured pre-operatively and post-operatively.

Eligibility criteria: Inclusion Criteria:

* Infants and Children undergoing cardiac surgery with cardiopulmonary bypass

Exclusion Criteria:

* Antibiotics, surgery, or chemotherapy within the past 8 weeks
* Continuous enteral feeds before surgery
* GI pathology or intestinal surgery (excluding G-tube)
* Liver disease with elevated transaminitis or dialysis-dependent renal disease

Primary outcomes:
measure: Combined Incidence of Adverse Events and Serious Adverse Events with Butyric Acid (SunButyrate-TG) Supplementation
timeFrame: 3 years
measure: Tolerance of SunButyrate-TG
timeFrame: Baseline to 3 weeks
measure: Changes to White Blood Cell Count with SunButyrate-TG Supplementation
timeFrame: Baseline to 3 weeks
measure: Changes to Hematocrit with SunButyrate-TG
timeFrame: Baseline to 3 weeks
measure: Changes in Platelets with SunButyrate-TG
timeFrame: Baseline to 3 weeks
measure: Changes to Renal Function (BUN, Creatinine or urine output) with SunButyrate-TG
timeFrame: Baseline to 4 months
measure: Changes in Liver Function with SunButyrate-TG
timeFrame: Baseline to 4 months
measure: Improvement in Gut Microbiome as Measured by Alpha Diversity, Shannon Diversity Index and Simpson Diversity Index with SunButyrate-TG Supplementation
timeFrame: Baseline to 4 months
measure: Changes in Short-Chain Fatty Acids with SunButyrate-TG
timeFrame: Baseline to 4 months
measure: Gut Barrier Function after SunButyrate-TG
timeFrame: Baseline to 4 months
Secondary outcomes:
measure: Reduction of Post-Operative Cytokine Values
timeFrame: Pre-surgery to 4 days post-operatively
measure: Changes in Neutrophils After Surgery with SunButyrate-TG
timeFrame: Pre-surgery to 4 days post-operatively
measure: Changes in Macrophages After Surgery with SunButyrate-TG
timeFrame: Pre-surgery to 4 days post-operatively
measure: Changes in T-regulatory Cells After Surgery with SunButyrate-TG
timeFrame: Pre-surgery to 4 days post-operatively
measure: Changes in Natural Killer T-cells Cells After Surgery with SunButyrate-TG
timeFrame: Pre-surgery to 4 days post-operatively
Other outcomes:
measure: Changes in Inflammatory Gene Activation
timeFrame: Pre-surgery to 4 days post-operatively
Locations:
city: Omaha
country: United States
facility: Children's Nebraska, 8200 Dodge St
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Jeffrey Salomon, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: