An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse

NCT05306925 | Recruiting

• 1 other identifier: UoL001648
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Preterm; Surgery; Nutritional Deficiency; Immune System and Related Disorders

Keywords

Neonate; Arginine; Postoperative; Immune function; Nutrition

Outcome Measures

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.

  Day 3 and 10 post-surgery

Secondary Outcomes (9)

• Gene expression via Illumina RNA sequencing

  Days 3, 10 and 30 post-surgery

• Gene expression via Illumina RNA sequencing

  Days 3, 10 and 30 post-surgery

• Gene expression via Illumina RNA sequencing

  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

Study Arms (3)

Standard parenteral nutrition

NO INTERVENTION

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)

EXPERIMENTAL

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.

Dietary Supplement: Arginine

Arginine supplementation (oral only)

EXPERIMENTAL

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.

Dietary Supplement: Arginine

Interventions

Arginine DIETARY_SUPPLEMENT

The 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%.

Arginine supplementation (combined); Arginine supplementation (oral only)

Eligibility Criteria

• Age: 22 Weeks - 44 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Liverpool: lead

Study Sites (2)

Alder Hey Children's Hospital

Liverpool, Merseyside, L14 5AB, United Kingdom

RECRUITING

Liverpool Women's Hospital

Liverpool, Merseyside, L8 7SS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Premature Birth; Malnutrition

Interventions

Arginine

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Central Study Contacts

Colin Morgan

CONTACT

+441517089988; colin.morgan@lwh.nhs.uk

Frances Callaghan

CONTACT

+441517089988; frances.callaghan@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is not blinded or randomized.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There will be parallel assignment of supplemented parenteral nutrition (PN) and standard parenteral nutrition dependent upon stock availability of intervention PN.

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: April 14, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)