An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse (ASPIRE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Gene expression via Illumina RNA sequencing
研究概览
简要总结
ASPIRE is a nutrition study focusing on the effect of arginine supplementation on immune function in postoperative infants.
The investigators will explore the effect of current intravenous feeding (parenteral nutrition (PN)) formulations and oral arginine supplementation on blood arginine levels and the genes that are involved in body nutrition and fighting infection in babies who have had major bowel surgery or been diagnosed with necrotising enterocolitis. The investigators will undertake an exploratory physiological study across two sites under which are part of a single neonatal partnership. 48 infants will be recruited; 24 preterm infants and 24 term/near term infants. 16 of these infants (8 preterm and 8 term/near term) will be supplemented with arginine in both oral and parenteral form, 16 infants will receive arginine supplementation in oral form alone and 16 infants will receive standard nutrition with no arginine supplement. The investigators will record nutritional intake and routine biochemical testing data (which includes amino acid levels) collected over the first 30 days post surgery or post NEC diagnosis. The investigators will take blood for analysis at prespecified intervals for RNA sequencing, ammonia and metabolomics. RNA sequencing findings will allow the investigators to describe the effect of arginine on gene activity in postoperative infants
The investigators hypothesise that arginine supplementation will result in changes in gene expression that are consistent with changes in T-cell function and associated inflammatory pathways.
详细描述
Title:
Arginine Supplementation and the Postoperative Immune REsponse (ASPIRE) in neonates
Population:
Preterm infants <30 weeks gestation requiring a laparotomy/major bowel surgery or diagnosed with necrotising enterocolitis (Modified Bell's Stage II or higher) before discharge before discharge ; Term and near term infants (born >35 weeks gestation) requiring a laparotomy/major bowel surgery in the first 3 days of life (gastroschisis; major bowel atresias expected to require at least 7 days PN).
Number of infants:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
This is not blinded or randomized.
入排标准
- 年龄范围
- 22 Weeks 至 44 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants born <30 weeks gestation requiring laparotomy/major bowel surgery or diagnosed with necrotising enterocolitis (Modified Bell's Stage II or higher) before discharge
- •Term and near term infants (born>35 weeks gestation) requiring laparotomy/major bowel surgery in the first 3 days of life (gastroschisis; major bowel atresias expected to require at least 7 days of PN)
排除标准
- •Infants who are unlikely to survive because of poor immediate postoperative condition
- •Infants known (or suspected to have) a diagnosis of inborn error of metabolism or serious liver dysfunction
- •Parents who are unable to give informed consent
研究组 & 干预措施
Standard parenteral nutrition
These infants will form the control group and will receive standard parenteral nutrition. They will be sub-stratified into gestational brackets - preterm (born <30 weeks) and term/near term.
Arginine supplementation (combined)
These infants will form an intervention group and will receive parenteral nutrition with additional arginine (up to 18% of amino acid make-up) for up to 14 days post-op and oral arginine supplementation up to 30 days post-op. They will be sub-stratified into gestational brackets - preterm (born <30 weeks) and term/near term.
干预措施: Arginine (Dietary Supplement)
Arginine supplementation (oral only)
These infants will form an intervention group and will receive standard parenteral nutrition and oral arginine supplementation up to 30 days post-op. They will be sub-stratified into gestational brackets - preterm (born <30 weeks) and term/near term.
干预措施: Arginine (Dietary Supplement)
结局指标
主要结局
Gene expression via Illumina RNA sequencing
时间窗: Day 3 and 10 post-surgery
RNA will be extracted from whole blood and sent for Illumina RNA sequencing. These sequences are then mapped to reference gene sets for gene expression analysis. The pattern of alteration in gene expression between days 3 and 10 in arginine deficient postoperative infants after correction of their deficiency by supplementation with arginine will be analysed. The changes in gene expression will be compared with those seen in unsupplemented infants. The genes of interest are those involved in T-cell function and associated inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
次要结局
- Body composition measuring fat free mass in grams(Days 3, 10 and 30 post-surgery)
- Plasma proline levels(Days 3, 10 and 30 post-surgery)
- Growth measuring body weight in grams(Days 3, 10 and 30 post-surgery)
- Body composition measuring total body fluid measured in litres(Days 3, 10 and 30 post-surgery)
- Blood ammonia levels(Days 3, 10 and 30 post-surgery)
- Plasma arginine levels(Days 3, 10 and 30 post-surgery)
- Gene expression via Illumina RNA sequencing(Days 3, 10 and 30 post-surgery)