PretermPAINT18NCT05299112
An Exploratory Study of Increased Preterm Arginine INTake (PAINT18)
A study testing Arginine in people with Preterm and Nutritional Deficiency, run by Liverpool Women's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
PAINT18 is a nutrition study focusing on the effect of arginine supplementation on immune function in preterm infants. The investigators will explore the effect of current intravenous feeding (parenteral nutrition (PN) formulations on blood arginine levels and the genes that are involved in body nutrition and fighting… Read more about this study
- Who is it for?
- Ages 22 to 29 weeks
- Conditions the study is for
- Preterm, Nutritional Deficiency, Immune System and Related Disorders
- What is being tested?
- Arginine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Dec 2021to 30 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 29 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants born <29 weeks' gestation
- and/or with birthweight <1200g
- Admitted to the Neonatal Unit at Liverpool Women's Hospital within 48 hours of birth.
Who cannot join
- Infants who are unlikely to survive the first week after birth.
- 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
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Liverpool Women's Hospital
Liverpool, Merseyside, L8 7SS
Louise Hardman, 00441517024346, louise.hardman@lwh.nhs.uk
Frances Callaghan, MBChB, frances.callaghan@nhs.net
About this study
Official title: An Exploratory Study of Increased Preterm Arginine INTake on Biological Pathways Affecting Immune Function in Infants Requiring Early Parenteral Nutrition
PAINT18 is a nutrition study focusing on the effect of arginine supplementation on immune function in preterm infants.
The investigators will explore the effect of current intravenous feeding (parenteral nutrition (PN) formulations on blood arginine levels and the genes that are involved in body nutrition and fighting infection in premature babies. The investigators will also investigate the effect of supplementing arginine on these genes. The investigators will undertake a single centre exploratory physiological study in 24 very premature infants receiving PN. 16 of these infants will be supplemented with arginine. The investigators will record nutritional intake and routine biochemical testing data (which includes amino acid levels) collected over the first 30 days of life. The investigators will take blood for analysis at prespecified intervals for RNA sequencing, ammonia and IGF-1 levels. RNA sequencing findings will allow the investigators to describe the effect of arginine on gene activity in preterm 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 The effect of increased Preterm Arginine INTake on biological pathways affecting immune function in infants requiring early parenteral nutrition (PAINT-18 )
Population Preterm infants <29 weeks gestation and/or <1200g
Number of infants 24 infants (completing the study) will be recruited over approximately 12 months
Number of sites One. Infants will be born at Liverpool Women's Hospital (LWH) or transferred to LWH within 48 hours of birth.
Study duration Informed consent will take place antenatally, where possible, or within 72 hours of birth. The first study related blood sample will be taken on day 3 of life with the last sample taken on day 30 of life. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).
Study intervention All infants will receive standard clinical treatment. 8 infants will receive PN with Vaminolact as the amino acid base, with 6.3% arginine content, and 16 infants will receive PN with additional arginine in the PN bag at a concentration of 18%. These 16 infants will be sub-stratified into two groups based on gestational age (23-26 weeks and 27-29 weeks).
Primary objective To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between day 3 and day 10 of life. This 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 infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
Secondary objectives
- To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between days 3, 10 and day 30 of life. This will be done via illumina RNA sequencing and statistical pathway analysis. The changes in gene expression will be compared with those seen between days 3, 10 and day 30 in unsupplemented infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
- Statistical pathway analysis will be used to identify genes and their relationship with key 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 compare the changes in metabolomic profiles of control and intervention infants during the first 30 days of life.
- To compare growth (weight and head circumference) and body composition data including total body water (intracellular and extracellular distribution) and fat free mass during study period
- Being tested
- Arginine
- Keywords
- Preterm, Arginine, 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 parenteral nutrition contains additional arginine (18% arginine content) as compared to standard parenteral nutrition (6.3% arginine content).
| 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 infants <27 weeks and infants >27 weeks gestation. |
| Arginine supplementation | Experimental | These infants will form the intervention group and will receive parenteral nutrition with additional arginine (18% of amino acid) for up to 14 days of life. They will be sub-stratified into infants <27 weeks and infants >27 weeks gestation. 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 preterm 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 of life
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 preterm 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 of life
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 preterm 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: Day 3, 10 and 30 of life
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 preterm 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: Day 3, 10 and 30 of life
Blood ammonia levels
Blood ammonia levels will be measured at day 3, 10 and 30 of life and levels in supplemented intervention infants will be compared to unsupplemented control infants.
Measured: Day 3, 10 and 30 of life
Plasma arginine levels
Plasma arginine levels will be measured at day 3, 10 and 30 of life and levels in supplemented intervention infants will be compared to unsupplemented control infants.
Measured: Day 3, 10 and 30 of life
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 of life. Metabolomics profiling and analysis will be used to compare supplemented intervention infants with unsupplemented control infants.
Measured: Day 3, 10 and 30 of life
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: Day 3, 10 and 30 of life
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: Day 3, 10 and 30 of life
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: Day 3, 10 and 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2022
- Study start7 Dec 2021
- Primary completion7 Jun 2023
- Study completion30 Jun 2025 (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
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liverpool Women's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool, University of California, Davis
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05299112
- Sponsor's protocol ID
- LWH1213
- Acronym
- PAINT18
- Status last verified
- Sep 2023
- First submitted
- 15 Feb 2022
- Last updated
- 6 Sep 2023
- 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 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of Increased Preterm Arginine INTake on Biological Pathways Affecting Immune Function in Infants Requiring Early Parenteral Nutrition
- ClinicalTrials.gov ID
- NCT05299112
- Acronym / sponsor ID
- PAINT18 / LWH1213
- Keywords
- Preterm, Arginine, Immune function, Nutrition
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Liverpool Women's NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Liverpool, University of California, Davis
- Study start
- 7 Dec 2021 (actual)
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 28 Mar 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.
PAINT18 is a nutrition study focusing on the effect of arginine supplementation on immune function in preterm infants.
The investigators will explore the effect of current intravenous feeding (parenteral nutrition (PN) formulations on blood arginine levels and the genes that are involved in body nutrition and fighting infection in premature babies. The investigators will also investigate the effect of supplementing arginine on these genes. The investigators will undertake a single centre exploratory physiological study in 24 very premature infants receiving PN. 16 of these infants will be supplemented with arginine. The investigators will record nutritional intake and routine biochemical testing data (which includes amino acid levels) collected over the first 30 days of life. The investigators will take blood for analysis at prespecified intervals for RNA sequencing, ammonia and IGF-1 levels. RNA sequencing findings will allow the investigators to describe the effect of arginine on gene activity in preterm 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 The effect of increased Preterm Arginine INTake on biological pathways affecting immune function in infants requiring early parenteral nutrition (PAINT-18 )
Population Preterm infants <29 weeks gestation and/or <1200g
Number of infants 24 infants (completing the study) will be recruited over approximately 12 months
Number of sites One. Infants will be born at Liverpool Women's Hospital (LWH) or transferred to LWH within 48 hours of birth.
Study duration Informed consent will take place antenatally, where possible, or within 72 hours of birth. The first study related blood sample will be taken on day 3 of life with the last sample taken on day 30 of life. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).
Study intervention All infants will receive standard clinical treatment. 8 infants will receive PN with Vaminolact as the amino acid base, with 6.3% arginine content, and 16 infants will receive PN with additional arginine in the PN bag at a concentration of 18%. These 16 infants will be sub-stratified into two groups based on gestational age (23-26 weeks and 27-29 weeks).
Primary objective To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between day 3 and day 10 of life. This 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 infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
Secondary objectives
- To examine the changes in gene expression present in arginine supplemented infants <29 weeks' gestation and/or <1200g between days 3, 10 and day 30 of life. This will be done via illumina RNA sequencing and statistical pathway analysis. The changes in gene expression will be compared with those seen between days 3, 10 and day 30 in unsupplemented infants. The genes of interest are those involved in immune function and inflammatory pathways. Statistical pathway analysis will be used to identify these genes and their relationship with key biological pathways.
- Statistical pathway analysis will be used to identify genes and their relationship with key 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 compare the changes in metabolomic profiles of control and intervention infants during the first 30 days of life.
- To compare growth (weight and head circumference) and body composition data including total body water (intracellular and extracellular distribution) and fat free mass during study period
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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 infants <27 weeks and infants >27 weeks gestation. |
| Arginine supplementation | Experimental | Dietary Supplement: ArginineThese infants will form the intervention group and will receive parenteral nutrition with additional arginine (18% of amino acid) for up to 14 days of life. They will be sub-stratified into infants <27 weeks and infants >27 weeks gestation. |
Who may qualify
- Ages
- 22 to 29 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Infants born <29 weeks' gestation
- and/or with birthweight <1200g
- Admitted to the Neonatal Unit at Liverpool Women's Hospital within 48 hours of birth.
Key exclusion criteria (3 listed)
- Infants who are unlikely to survive the first week after birth.
- 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 parenteral nutrition contains additional arginine (18% arginine content) as compared to standard parenteral nutrition (6.3% arginine content). | Dietary supplement | Arginine supplementation |
Primary outcome
Gene expression via Illumina RNA sequencing
Time frame: Day 3 and 10 of life
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 preterm 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 of life
Gene expression via Illumina RNA sequencing
Time frame: Day 3, 10 and 30 of life
Gene expression via Illumina RNA sequencing
Time frame: Day 3, 10 and 30 of life
Blood ammonia levels
Time frame: Day 3, 10 and 30 of life
Plasma arginine levels
Time frame: Day 3, 10 and 30 of life
Plasma proline levels
Time frame: Day 3, 10 and 30 of life
Body composition measuring total body fluid measured in litres
Time frame: Day 3, 10 and 30 of life
Body composition measuring fat free mass in grams
Time frame: Day 3, 10 and 30 of life
Growth measuring body weight in grams
Time frame: Day 3, 10 and 30
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Individual participant dataSharing planned: No. No IPD will be made available
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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. This study is not recruiting at the moment.
1 site 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 Nutritional Deficiency, run by Liverpool Women's NHS Foundation Trust at 1 site 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 3 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: status not confirmed, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. 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 of life). 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 6 Sep 2023.