Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

Официальное название

Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids, A Phase IIa Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 2 mL SunButyrate-TG
  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.
• Препарат Placebo
  Participants randomized into the Placebo arm will take the oil-based placebo once daily for 3 weeks prior to cardiac surgery
• Препарат 4 mL SunButyrate-TG
  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.

Первичные конечные точки

• Combined Incidence of Adverse Events and Serious Adverse Events with Butyric Acid (SunButyrate-TG) Supplementation [Срок оценки: 3 years]
• Tolerance of SunButyrate-TG [Срок оценки: Baseline to 3 weeks]
• Changes to White Blood Cell Count with SunButyrate-TG Supplementation [Срок оценки: Baseline to 3 weeks]
• Changes to Hematocrit with SunButyrate-TG [Срок оценки: Baseline to 3 weeks]
• Changes in Platelets with SunButyrate-TG [Срок оценки: Baseline to 3 weeks]
• Changes to Renal Function (BUN, Creatinine or urine output) with SunButyrate-TG [Срок оценки: Baseline to 4 months]
• Changes in Liver Function with SunButyrate-TG [Срок оценки: Baseline to 4 months]
• Improvement in Gut Microbiome as Measured by Alpha Diversity, Shannon Diversity Index and Simpson Diversity Index with SunButyrate-TG Supplementation [Срок оценки: Baseline to 4 months]
• Changes in Short-Chain Fatty Acids with SunButyrate-TG [Срок оценки: Baseline to 4 months]
• Gut Barrier Function after SunButyrate-TG [Срок оценки: Baseline to 4 months]

Вторичные конечные точки (5)

• Reduction of Post-Operative Cytokine Values [Срок оценки: Pre-surgery to 4 days post-operatively]
• Changes in Neutrophils After Surgery with SunButyrate-TG [Срок оценки: Pre-surgery to 4 days post-operatively]
• Changes in Macrophages After Surgery with SunButyrate-TG [Срок оценки: Pre-surgery to 4 days post-operatively]
• Changes in T-regulatory Cells After Surgery with SunButyrate-TG [Срок оценки: Pre-surgery to 4 days post-operatively]
• Changes in Natural Killer T-cells Cells After Surgery with SunButyrate-TG [Срок оценки: Pre-surgery to 4 days post-operatively]

Критерии участия

Критерии включения

• Infants and Children undergoing cardiac surgery with cardiopulmonary bypass

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Children's Nebraska, 8200 Dodge St — Omaha

Идентификаторы

NCT: NCT06882772 · 0839-24-FB · 11543

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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