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.
Infants and Children undergoing cardiac surgery with cardiopulmonary bypass
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
Parallel
2 mL SunButyrate-TG
DrugParticipants randomized into the 2 milliliter (mL) SunButyrate-TG will take the supplement once daily for 3 weeks prior to cardiac surgery. Note: This is a Dietary Supplement, but the FDA requires an Investigational New Drug (IND) number because inflammation is being treated.
Placebo
DrugParticipants randomized into the Placebo arm will take the oil-based placebo once daily for 3 weeks prior to cardiac surgery
4 mL SunButyrate-TG
DrugParticipants randomized into the 4 mL SunButyrate-TG arm will take the supplement once daily for 3 weeks prior to cardiac surgery. Note: This is a Dietary Supplement, but the FDA requires an Investigational New Drug (IND) number because inflammation is being treated.
Combined Incidence of Adverse Events and Serious Adverse Events with Butyric Acid (SunButyrate-TG) Supplementation
Safety will be measured by the combined incidence of adverse events (AE) and serious adverse events (SAE). These include allergic reaction, vomiting, diarrhea, abdominal distention, infection, hospitalization, or any other concern the families report. A Data Safety Monitoring Board (DSMB) will review and catalog the incidence and severity to determine study continuation. Investigators will evaluate each AE/SAE to determine the safety of the supplement in this age and participant population. AE and SAE definitions used according to FDA regulations. A scoring system of 1-5 will be used to determine the severity of the AE after review by the DSMB. A cumulative score of 3 or greater will require cessation of the study for that individual. If an accumulation of 20 participants or more have a score \>3 the study will be stopped. If an accumulation of SAE (score of 5) in 8 or more participants, the study will be stopped.
Tolerance of SunButyrate-TG
Tolerance will be measured by the incidence of nausea, inability to consume the supplement, or parental concern of intolerance. The tolerance scoring metric will be used to aggregate the listed criteria into a score for each participant. Each characteristic will receive a point. If a participant has a score of 2 or greater, it will be defined as intolerance. Participant study continuation will be discussed with the family in weekly calls during the supplementation period.
Changes to White Blood Cell Count with SunButyrate-TG Supplementation
Safety will be evaluated through measurement of the white blood cell (WBC) count of the complete blood cell (CBC) count. Investigators will evaluate changes between the pre- and post-supplementation period CBC looking at changes in WBC count to quantify the incidence of leukocytosis (WBC \> 15.0 x 10\^9/L) and leukopenia (WBC \< 6.0 x 10\^9/L) after completing the supplement and prior to the surgery. Any participant that has a WBC count higher or lower than the values stated above will be documented.
Changes to Hematocrit with SunButyrate-TG
Investigators will measure hematocrit between pre- and post-supplement time points to determine the effect of SunButyrate-TG. Investigators will evaluate changes between the pre- and post-supplementation period complete blood count (CBC) looking at changes in of anemia (hematocrit \< 29%) or polycythemia (hematocrit \> 45%) after completing the supplement and prior to the surgery. Any participant that has a hematocrit higher or lower than the values stated above will be documented.
Reduction of Post-Operative Cytokine Values
Investigators will measure cytokine levels pre- and post-surgery to determine changes in cytokine profiles of a panel of 8 different cytokines, including TNF-alpha, IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, TGF-beta and IFN-gamma). An improvement in the cytokine profile will be considered if there is a statistically significant reduction in pro-inflammatory cytokines (IL-1, TNFa, IL-6, IL-4, or IL-8, IFN-gamma) or a significant increase in anti-inflammatory cytokines (IL-10 and TGF-beta) compared to the placebo group. These cytokines are measured together and will be considered a positive improvement in cytokine profiles if at least 2 pro-inflammatory cytokine values are reduced in conjunction with an increase in IL-10 and/or TGF-beta.
Changes in Neutrophils After Surgery with SunButyrate-TG
Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in neutrophils. A significant change will be considered if there is a reduction of greater than 5% total neutrophil count via flow cytometry.
Changes in Macrophages After Surgery with SunButyrate-TG
Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in macrophages. A significant change will be considered if there is a reduction of greater than 5% total macrophage count via flow cytometry.
Changes in T-regulatory Cells After Surgery with SunButyrate-TG
Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in T-regulatory cells (T-cell). A significant change will be considered if there is an increase of greater than 10% in T-regulatory cell count via flow cytometry.
Changes in Inflammatory Gene Activation
Investigators will measure inflammatory genes using an ribonucleic acid (RNA) hybridization panel and evaluate the level of activation of these genes pre-and post-surgery to determine a decrease in inflammatory signaling following supplementation with SunButyrate-TG compared to placebo. These inflammatory gene profiles are identified as a panel are are unable to be separated out. The entirety of the inflammatory gene profile will be evaluated together to assess changes in inflammatory gene activation.
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