An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age22-44
SponsorUniversity of Liverpool
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Arginine
Dietary supplementThe intervention infants will receive either parenteral nutrition which contains additional arginine (up to 18% arginine content) or a separate arginine infusion to provide up to 18% arginine. This is in comparison to standard parenteral nutrition which has an arginine content of 6.3%.
Treatment groups
48 Participants
are divided into 3 treatment groupsGroup A: Standard parenteral nutritionNo intervention 0 interventions
Group B: Arginine supplementation (combined)Experimental treatment 1 intervention
Group C: Arginine supplementation (oral only)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Gene expression via Illumina RNA sequencing
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.
Time frame
Day 3 and 10 post-surgerySecondary outcomes
1
Gene expression via Illumina RNA sequencing
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, 10 and 30 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. Secondary analysis will include Day 30 measurements.
Time frame
Days 3, 10 and 30 post-surgery2
Gene expression via Illumina RNA sequencing
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, 10 and 30 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 known to be associated with necrotising enterocolitis (NEC). Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
Time frame
Days 3, 10 and 30 post-surgery3
Gene expression via Illumina RNA sequencing
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, 10 and 30 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 known to be involved with arginine metabolism. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
Time frame
Days 3, 10 and 30 post-surgery4
Blood ammonia levels
Blood ammonia levels will be measured at day 3, 10 and 30 post-surgery and levels in supplemented intervention infants will be compared to unsupplemented control infants.
Time frame
Days 3, 10 and 30 post-surgerySponsors and contacts
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Source ClinicalTrials.gov