Preterm Arginine INTake Study (PAINT)

Effect of Preterm Arginine INTake on Biological Pathways Affecting Immune Function in Infants Requiring Early Parenteral Nutrition

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. They will also investigate the effect of supplementing arginine on these genes. The investigators will undertake a single centre exploratory physiological study in 12 very premature infants receiving PN. 4 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 10 days of life. They will take blood for analysis at prespecified intervals for microarray, ammonia and IGF-1 levels. Microarray findings will allow the investigators to describe the effect of arginine on gene activity in preterm infants.

Study Overview

• Status: Completed
• Conditions: Preterm Infant Nutrition and Immune Function
• Intervention / Treatment: Dietary supplement: Arginine

Detailed Description

Title:

Effect of Preterm Arginine INTake on biological pathways affecting immune function in infants requiring early parenteral nutrition (PAINT)

Population: Preterm infants <29 weeks gestation

Number of infants: 12 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 within 72 hours of birth. The first study related blood sample will be taken at this point and will determine arginine status (using blood ammonia and arginine levels) with the last sample taken on postnatal day 10. Other study assessments reflect those routinely performed in preterm infants receiving parenteral nutrition (PN).

Study intervention: All infants will receive standard clinical treatment. The study will involve 4 infants with normal arginine status, and 8 infants with evidence of arginine deficiency. Of these, 4 infants will receive standard PN and the study intervention of an additional arginine infusion of 10mg/kg/hr from day 3 until day 10, the other 8 infants will receive standard PN only.

Primary objective: To determine the alterations in gene expression present in infants <29 weeks gestation (and shown to be arginine deficient on day 3) between day 3 and day 10 in infants receiving additional arginine supplementation. The changes in gene expression will be compared with those seen between day 3 and day 10 in unsupplemented infants, with and without arginine deficiency. The genes of interest are those involved in T-cell function and associated 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 assess whether there is an association between high ammonia levels (as a measure of functional arginine deficiency) and T-cell dysfunction and associated inflammatory pathways.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L8 7SS
    • Liverpool Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterm infants born between 23 and 29 completed weeks gestation and admitted to the neonatal unit within 48 hours of birth

Exclusion Criteria:

• Infants who are unlikely to survive the first week after birth.
• Infants with early onset infection (<72 hours)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Low Arginine unsupplemented; These infants identified as having low blood arginine levels will receive standard care.
EXPERIMENTAL: Low Arginine supplemented; These infants identified as having low arginine levels will receive an additional arginine infusion between days 3 and 10 of life.	Dietary supplement: Arginine
NO_INTERVENTION: Normal Arginine; These infants identified as having normal arginine levels will receive standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pattern of alteration in gene expression between day 3 and day 10 in arginine deficient preterm infants after supplementation with arginine.	The changes in gene expression will be compared with those seen in unsupplemented infants, with and without arginine deficiency. The genes of interest are those involved in T-cell function and associated inflammatory pathways.	Samples on Day 3 and Day 10 of life

Secondary Outcome Measures

Outcome Measure	Time Frame
The pattern of alteration in gene expression associated with biological pathways known to be associated with NEC.	Day 3 and Day 10 of life
The pattern of alteration in gene expression associated with biological pathways known to be involved in arginine metabolism	Day 3 and Day 10 of life
The pattern of alteration in gene expression associated with biological pathways that are related to the IGF-1-insulin axis	Day 3 and Day 10 of life
To validate if high ammonia levels (as a measure of functional arginine deficiency) are linked with impaired T-cell function and associated inflammatory pathways	Day 3 of life

Collaborators and Investigators

• Sponsor: Liverpool Women's NHS Foundation Trust
• Investigators: Study Director: Colin Morgan, MBBS BSc MD, Neonatal Unit, Liverpool Women's Hospital, Crown St, Liverpool, L8 7SS

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 5, 2016
• Primary Completion (ACTUAL): July 31, 2017
• Study Completion (ACTUAL): March 31, 2018

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (ESTIMATE): April 26, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: nutrition; preterm; immune function; arginine
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: LWH1077

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be made available