An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse

NCT ID: NCT05306925

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-14

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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:

48 infants (completing the study) will be recruited over approximately 24-36 months: 24 in the preterm group and 24 in the term group.

Number of sites:

Two sites - Alder Hey Children's Hospital (AHCH) and Liverpool Women's Hospital (LWH) under the umbrella of the Neonatal Partnership. Eligible infants will undergo surgery at AHCH and will receive early postoperative care at either AHCH or LWH

Study duration:

Informed consent will take place preoperatively where possible, or within 5 days of surgery or NEC diagnosis. In the term group, antenatal recruitment will be attempted. The first study related blood sample will be taken as soon as possible postoperatively following consent with the last sample taken on day 30 post-operatively. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).

Study intervention:

All infants will receive standard clinical treatment. 8 preterm and 8 term infants will receive PN as determined by local clinical guidelines (6.3 or 8.4% arginine content). 8 term infants and 8 preterm infants will receive PN as determined by local clinical guidelines (6.3 or 8.4% arginine content) and enteral arginine supplementation. Enteral L-arginine will start with the first enteral feedings: starting 0.75mmol/kg/day, doubled to 1.5mmol/kg (261mg/kg/day) when reaching 40% of enteral feeds. 8 preterm and 8 term infants will receive PN with an additional arginine supplement and oral supplementation. PN supplementation will aim to achieve up to 18% arginine intake (allocated according to intervention PN stock availability) and will be titrated against oral supplementation during the transition to enteral feeds.

Primary objective:

To examine the changes in gene expression present in arginine supplemented infants between day 3 and day 10 post-operatively. Thus will be done via illumina RNA sequencing and statistical pathway analysis. The changes in gene expression will be compared with those seen between day 3 and day 10 in unsupplemented preterm and term infants. The genes of interest are those involved in immune function and inflammatory pathways.

Secondary objectives:

1. To explore other biological pathways i) known to be involved in the pathogenesis of necrotising enterocolitis ii) involved in arginine metabolism iii) that are related to the insulin-IGF-I axis
2. To determine the changes in metabolomic profiles of these infants during the first 30 days postoperatively.
3. Growth and body composition data during study period.

Conditions

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Preterm Surgery Nutritional Deficiency Immune System and Related Disorders

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

There will be parallel assignment of supplemented parenteral nutrition (PN) and standard parenteral nutrition dependent upon stock availability of intervention PN.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

This is not blinded or randomized.

Study Groups

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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.

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type EXPERIMENTAL

Arginine

Intervention Type 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 (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.

Group Type EXPERIMENTAL

Arginine

Intervention Type 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%.

Interventions

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Arginine

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%.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

22 Weeks

Maximum Eligible Age

44 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Liverpool

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Alder Hey Children's Hospital

Liverpool, Merseyside, United Kingdom

Site Status RECRUITING

Liverpool Women's Hospital

Liverpool, Merseyside, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Colin Morgan

Role: CONTACT

+441517089988

Frances Callaghan

Role: CONTACT

+441517089988

Facility Contacts

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Emma Rutherford

Role: primary

01512284811

Louise Hardman

Role: primary

01517024346

Other Identifiers

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UoL001648

Identifier Type: -

Identifier Source: org_study_id

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