Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

NCT06882772 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 0839-24-FB11543
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Heart Disease (CHD)

Keywords

Congenital Heart Disease; Gut Health; Microbiome; Gut Barrier Function; Inflammation

Outcome Measures

Primary Outcomes (10)

• 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.

  3 years

• 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.

  Baseline to 3 weeks

• 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.

  Baseline to 3 weeks

• 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.

  Baseline to 3 weeks

• Changes in Platelets with SunButyrate-TG

  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 complete blood count looking at changes in platelet (PLT) count to quantify the incidence of thrombocytopenia (PLT \< 30 x 10\^9/L) or thrombocythemia (PLT \> 750 x 10\^9/L). Any participant that has a PLT count higher or lower than the values stated above will be documented.

  Baseline to 3 weeks

• Changes to Renal Function (BUN, Creatinine or urine output) with SunButyrate-TG

  Investigators will collect blood for a comprehensive metabolic panel before and after supplementation with SunButyrate-TG. Investigators will evaluate the changes in blood urea nitrogen (BUN) and Creatinine to determine evidence of renal impairment or acute kidney injury based upon Kidney Disease: Improving Global Outcomes (KDIGO) criteria (creatinine increase 1.5-1.9 times baseline or \>0.3 mg/dL increase), or urine output \< 0.5 mL/kg/h for 6-12 hours (excluding overnight for potty-trained children).

  Baseline to 4 months

• Changes in Liver Function with SunButyrate-TG

  Investigators will collect blood and measure a comprehensive metabolic panel before and after supplementation for evidence of liver injury. Investigators will determine: 1. Presence of acidosis (pH\< 7.3) 2. Elevation of transaminitis (AST/ALT \> 3 x baseline) 3. Elevation in INR (\>2 if not on coumadin) 4. Elevation in Bilirubin (\>2 mg/dL) 5. Elevation in alkaline phosphatase (\> 2 x baseline) If a participant meets any one of the above criteria, this will be considered evidence of liver injury and reported.

  Baseline to 4 months

• Improvement in Gut Microbiome as Measured by Alpha Diversity, Shannon Diversity Index and Simpson Diversity Index with SunButyrate-TG Supplementation

  Changes to the gut microbiome will be measured before and after supplementation, as well as post-operatively. Investigators will measure improvement in alpha diversity and the number of short-chain fatty acids (SCFA) producing bacterial populations. An improvement will be classified by an increase in alpha diversity of measurable OTU's by 12, Shannon diversity index (increase of 0.5), and Simpson diversity index (increase of 0.08), and specific number of SCFA producing organisms by 5 OTU's compared to the placebo group.

  Baseline to 4 months

• Changes in Short-Chain Fatty Acids with SunButyrate-TG

  Investigators will measure metabolite profiles to evaluate the amount of short-chain fatty acids (SCFA) in the gut and plasma before and after supplementation with SunButyrate-TG. This will be classified by a statistically significant increase (p\<0.05) in a list of 8 different SCFA. A positive increase in SCFA production will be classified by at least 1 SCFA being significantly increased following supplementation with SunButyrate-TG compared to the placebo group.

  Baseline to 4 months

• Gut Barrier Function after SunButyrate-TG

  Investigators will measure 3 plasma markers of intestinal barrier function between pre- and post-supplement, as well as post-operatively. These markers are claudin-2, claudin-3, and intestinal fatty acid binding protein (FABP2). An improvement in gut barrier will be considered if there is a statistically significant reduction in the plasma marker of any of these at the post-supplementation, or post-operative time points compared to the placebo group.

  Baseline to 4 months

Secondary Outcomes (5)

• Reduction of Post-Operative Cytokine Values

  Pre-surgery to 4 days post-operatively

• Changes in Neutrophils After Surgery with SunButyrate-TG

  Pre-surgery to 4 days post-operatively

• Changes in Macrophages After Surgery with SunButyrate-TG

  Pre-surgery to 4 days post-operatively

• Changes in T-regulatory Cells After Surgery with SunButyrate-TG

  Pre-surgery to 4 days post-operatively

• Changes in Natural Killer T-cells Cells After Surgery with SunButyrate-TG

  Pre-surgery to 4 days post-operatively

Other Outcomes (1)

• Changes in Inflammatory Gene Activation

  Pre-surgery to 4 days post-operatively

Study Arms (3)

2 mL SunButyrate-TG (Arm1)

EXPERIMENTAL

Participants will receive 2 milliliter (mL) SunButyrate-TG once daily for 3 weeks prior to cardiac surgery.

Drug: 2 mL SunButyrate-TG

4 mL SunButyrate-TG (Arm 2)

EXPERIMENTAL

Participants will receive 4 milliliter (mL) SunButyrate-TG once daily for 3 weeks prior to cardiac surgery.

Drug: 4 mL SunButyrate-TG

Placebo Comparator (Arm 3)

PLACEBO COMPARATOR

Participants will receive either 2 milliliter (mL) or 4 mL of an inactive oil-based placebo once daily for 3 weeks prior to cardiac surgery.

Drug: Placebo

Interventions

2 mL SunButyrate-TG DRUG

Participants 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.

Also known as: Butyrate Liquid Supplement

2 mL SunButyrate-TG (Arm1)

Placebo DRUG

Participants randomized into the Placebo arm will take the oil-based placebo once daily for 3 weeks prior to cardiac surgery

Also known as: sugar pill

Placebo Comparator (Arm 3)

4 mL SunButyrate-TG DRUG

Participants 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.

Also known as: Butyrate Liquid Supplement

4 mL SunButyrate-TG (Arm 2)

Eligibility Criteria

• Age: 1 Month - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants and Children undergoing cardiac surgery with cardiopulmonary bypass

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

Children's Nebraska, 8200 Dodge St

Omaha, Nebraska, 68114, United States

Location

MeSH Terms

Conditions

Heart Defects, Congenital; Inflammation

Interventions

Sugars

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Jeffrey Salomon, MD, MBA

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey D Salomon, MD, MBA

CONTACT

940-453-7166; jeffrey.salomon@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: March 19, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 24, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Information will be shared after completion of the study starting in 2029 and be available for 5 years.
• Access Criteria: Information will be shared upon request to the PI.

Locations

US (1)