PretermASPIRENCT05306925
An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse
A study testing Arginine in people with Preterm and Surgery, run by University of Liverpool at 2 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 22 to 44 weeks
- Conditions the study is for
- Preterm, Surgery, Nutritional Deficiency
- What is being tested?
- Arginine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 14 Apr 2022to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 44 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
Alder Hey Children's Hospital
Liverpool, Merseyside, L14 5AB
Emma Rutherford, 01512284811
Daniel Hawcutt
- Recruiting
Liverpool Women's Hospital
Liverpool, Merseyside, L8 7SS
Louise Hardman, 01517024346
Frances Callaghan, MBChB
About this study
Official title: An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse (ASPIRE)
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.
Read the detailed description
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:
- 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
- To determine the changes in metabolomic profiles of these infants during the first 30 days postoperatively.
- Growth and body composition data during study period.
- Being tested
- Arginine
- Keywords
- Neonate, Arginine, Postoperative, Immune function, Nutrition
- Medical subject headings
- Premature Birth, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArginineDietary 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%.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Arginine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 3 and 10 post-surgery
Secondary outcomes (9)
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.
Measured: Days 3, 10 and 30 post-surgery
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.
Measured: Days 3, 10 and 30 post-surgery
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.
Measured: Days 3, 10 and 30 post-surgery
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.
Measured: Days 3, 10 and 30 post-surgery
Plasma arginine levels
Plasma arginine 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.
Measured: Days 3, 10 and 30 post-surgery
Plasma proline levels
Proline is a urea cycle intermediate involved in arginine metabolism. Plasma proline levels will be measured at day 3, 10 and 30 post-surgery. Metabolomics profiling and analysis will be used to compare supplemented intervention infants with unsupplemented control infants.
Measured: Days 3, 10 and 30 post-surgery
Body composition measuring total body fluid measured in litres
Body composition measurements will be taken regularly via bioelectrical impedance measuring total body fluid (intracellular and extra cellular distribution) during the study period. Results from control and intervention infants will be compared.
Measured: Days 3, 10 and 30 post-surgery
Body composition measuring fat free mass in grams
Body composition measurements will be taken regularly via bioelectrical impedance measuring fat free mass during the study period. Results from control and intervention infants will be compared.
Measured: Days 3, 10 and 30 post-surgery
Growth measuring body weight in grams
Infants will be weighed regularly during the study period. Measurements from control and intervention infants will be compared.
Measured: Days 3, 10 and 30 post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start14 Apr 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PretermStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- There will be parallel assignment of supplemented parenteral nutrition (PN) and standard parenteral nutrition dependent upon stock availability of intervention PN.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306925
- Sponsor's protocol ID
- UoL001648
- Acronym
- ASPIRE
- Status last verified
- Feb 2026
- First submitted
- 23 Mar 2022
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No IPD will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of Arginine Supplementation and the Postoperative Immune REsponse (ASPIRE)
- ClinicalTrials.gov ID
- NCT05306925
- Acronym / sponsor ID
- ASPIRE / UoL001648
- Keywords
- Neonate, Arginine, Postoperative, Immune function, Nutrition
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Study start
- 14 Apr 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 1 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- 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
- To determine the changes in metabolomic profiles of these infants during the first 30 days postoperatively.
- Growth and body composition data during study period.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- There will be parallel assignment of supplemented parenteral nutrition (PN) and standard parenteral nutrition dependent upon stock availability of intervention PN.
| Arm | Type | Receives |
|---|---|---|
| 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 | Dietary Supplement: ArginineThese 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. |
| Arginine supplementation (oral only) | Experimental | Dietary Supplement: ArginineThese 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. |
Who may qualify
- Ages
- 22 to 44 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArginineThe 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%. | Dietary supplement | Arginine supplementation (combined), Arginine supplementation (oral only) |
Primary outcome
Gene expression via Illumina RNA sequencing
Time frame: 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.
9 secondary outcomes
Gene expression via Illumina RNA sequencing
Time frame: Days 3, 10 and 30 post-surgery
Gene expression via Illumina RNA sequencing
Time frame: Days 3, 10 and 30 post-surgery
Gene expression via Illumina RNA sequencing
Time frame: Days 3, 10 and 30 post-surgery
Blood ammonia levels
Time frame: Days 3, 10 and 30 post-surgery
Plasma arginine levels
Time frame: Days 3, 10 and 30 post-surgery
Plasma proline levels
Time frame: Days 3, 10 and 30 post-surgery
Body composition measuring total body fluid measured in litres
Time frame: Days 3, 10 and 30 post-surgery
Body composition measuring fat free mass in grams
Time frame: Days 3, 10 and 30 post-surgery
Growth measuring body weight in grams
Time frame: Days 3, 10 and 30 post-surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Individual participant dataSharing planned: No. No IPD will be made available.
Related trials for Preterm
Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Recruiting
Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Preterm Birth, Enterocolitis, Necrotizing
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
RecruitingObservational study
Multidimensional Dynamic Early Warning System for Neonatal Necrotizing Enterocolitis: A Multicenter Clinical Study
NEC - Necrotizing Enterocolitis
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arginine in people with Preterm and Surgery, run by University of Liverpool at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Colin Morgan (+441517089988, colin.morgan@lwh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gene expression via Illumina RNA sequencing (time frame: Day 3 and 10 post-surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.