Clinical trial NCT06486194: Preemie Milk Analyser Validation Study
Official title: Analytical Validation and Clinical Testing of the Preemie System for Analysis and Calculation of Targeted Fortification of Mother's Breast Milk for Preterm Infants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pre-Term
Breast Milk Expression
Nutrition Disorder, Infant
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Tellspec Ltd
First posted: 2024-07-03
Enrollment: 180
Sex: ALL
Minimum age (years): 0
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1: Validation of the Preemie sensor, encompassing 2 different analytical studies for assessing the accuracy (1) and the precision/reproducibility (2) of the system

Phase 2: Open label randomised controlled trial to test use of Preemie ecosystem in clinical practice for the delivery of targeted individualised breast milk fortification
Primary purpose: OTHER

Brief summary: This study aims to test and validate the Preemie Ecosystem- a new device and associated software package for measuring the nutrient (fat, protein and carbohydrate) content of the breast milk of the mothers of premature babies. This is potentially useful, as premature babies have higher nutritional requirements than babies born at term near their due date. At the moment, a nutritional supplement called breast milk fortifier is added to breast milk in standard amounts to improve its nutritional content and help premature babies grow. However, we know that each mother's breast milk is different, and varies from day to day, so each mother's milk may require more or less of such supplements in order to meet European recommendations for the nutrient intake.

The aim of this study is to first test and validate the accuracy of the Preemie device for measuring the nutritional content of mother's breast milk, using milk donated to the local donor milk bank and from mothers of babies currently on the neonatal unit. Next, once this is complete, the aim is to demonstrate it is feasible to use the Preemie device to enable fortification of mother's milk on an individualised basis for a small group of premature babies. The growth and nutrient intakes of these babies will be compared to another group who are cared for using the standard fortification approach.

The results of this study will be used to gain "Conformité Européenne" (CE) certification of the Preemie device and software.

Detailed description: This is a single centre study taking place in a neonatal intensive care unit which is a regional referral centre for neonatal surgery and other tertiary specialities. The centre has well established policies for nutritional care, inducing the routine use of breast milk fortifier, and a track record in research into the nutrition and growth of preterm infants. It will have 2 phases:

Phase 1: Validation of the Preemie sensor, encompassing 2 different analytical studies for assessing the accuracy (1) and the precision/reproducibility (2) of the system

Phase 2: Open label randomised controlled trial to test use of Preemie ecosystem in clinical practice for the delivery of targeted individualised breast milk fortification

The methods used in each phase are as follows:

PHASE 1: Validation of Preemie Sensor Part A - Mothers currently expressing breast milk and meeting the inclusion criteria will be approached to take part in the study. They will be asked to provide 120ml of their breast milk which will be divided into a 20ml sample for use with the Preemie system and a 100ml sample for formal laboratory testing. The 20ml will be divided into ten smaller 2ml samples, and these will have their nutrient content (energy, fat, carbohydrate/sugar and protein) measured each day (in triplicate) using the Preemie sensor over a five day period and results recorded. The 100ml sample will be sent away to an independent third-party external laboratory to have its nutrient content (energy, fat, carbohydrate and protein) measured using standardised laboratory methods and results returned back to the study team. The results from the 2 systems will then be compared and the Preemie sensor assessed for accuracy.

Part B - 5 mothers currently expressing milk and donating to Southampton Milk bank will be approached to take part in the study and asked to provide 170ml of their milk which will be divided into a 100ml sample for formal laboratory testing (see above). For reproducibility tests, the 5 milk samples (30 aliquots of 2 mL per sample for running the test, and 5 aliquots serving as back-up, for a total of 70 ml per sample) will be analysed in 3 different rooms, by 3 different operators, using independent Preemie units, over the 5-day precision study. The Preemie precision/reproducibility will be then assessed by measuring the standard deviation between day, within run, between run, and in total, at each site, for each analyte.

For purposes of this phase of the study a "human breast milk sample" is one provided by a mother from a single expression. A mother may provide more than one sample if her milk supply allows this (see inclusion criteria) but samples should be at least 3 weeks apart. Purposive sampling will be used to ensure that the source of the samples is spread equally across the following 3 groups:

* Mothers of preterm infants born before 37 weeks gestation
* Mothers of term infants less than 8 weeks old
* Mothers of term infants more than 8 weeks old

PHASE 2: Open label randomised controlled trial to test use of Preemie ecosystem in clinical practice for the delivery of targeted individualised breast milk fortification This phase will see if it is possible to recruit to a trial and deliver targeted fortification of breast milk for infants on the Neonatal Intensive Care Unit (NICU) to improve their growth and metabolism.

30 preterm infants will be recruited and randomised (chosen at random using a computer) to receive either targeted fortification or standard fortification. In the targeted fortification group, the nutritional content (energy, fat, carbohydrate and protein) of mothers breast milk (MBM) or Donor Breast Milk (DBM) for use in a days milk feeds will be measured using the Preemie sensor every 2-3 days, and the amounts of breast milk fortifier (BMF), Protein supplements, carbohydrate supplements and fat supplements needed to be added in order for that sample of milk to meet current 2022 European recommendations nutritional intake for preterm infants calculated by the Preemie Sensor NutriNTrack software. Feeds will be made up in batches of 24hrs worth of feeds each day based on these calculations and the resulting supplement amounts used for the next 2-3 days until another sample of MBM is analysed. This approach is in line with the research of other groups who have demonstrated this approach to be safe (using a different milk analyser). In the Standard fortification group Mother's breast milk (MBM) or Donor Breast Milk (DBM) for use in a days milk feeds will be measured using the Preemie sensor every 2-3 days and results recorded. MBM or DBM will then be fortified in the standard way according to the manufacturer's recommendations, which assume a standard macronutrient content of the milk The allocated fortification approach (targeted or standardised) will be continued until the infant no longer requires fortification (eg moves onto formula milk) or reaches 34 weeks (when they would begin to have some breast feeds), is transferred to another hospital, or discharged home At the end of the study the two sets of infants will be compared in terms of nutrient intakes and growth.

Staff involved in delivering the Targeted Fortification will also be asked to provide feedback on the ease of use of the Preemie Ecosystem through semi-structured interviews and focus groups. Staff may also be observed by research staff using the machine in order to understand any issues and improve ease of use and user experience.

Eligibility criteria: Inclusion criteria Phase 1A For University Hospital Southampton (UHS) milk bank donors

* Approved as a donor for the UHS milk bank through the usual process
* Be providing milk to UHS donor milk bank For mothers of infant inpatients
* Have an infant who is currently an inpatient in the neonatal unit, paediatric wards, paediatric cardiac ward, or paediatric intensive care unit
* Be providing breastmilk for their preterm or term born infant
* Have sufficient breast milk available such that providing 120ml breast milk for the study does not impact on the needs of their infant.

Inclusion criteria Phase 1B

* Approved as a donor for the UHS milk bank through the usual process
* Be providing milk to UHS donor milk bank

Exclusion criteria Phase 1A and 1B For mothers of infant inpatients

- Mothers whose infants are inpatients and where there is a concern about adequacy of maternal milk supply to feed their infant

Inclusion Criteria Phase 2

* Birth weight ≥1kg and \<1.8 kg (so meet the ESPGHAN criteria for breast milk fortification)
* Be taking fully fortified enteral breast milk feeds (≥150 ml/kg/day of mothers or donor breast milk containing breast milk fortifier as per the manufacturer's instructions)
* Tolerating fully fortified breast milk feeds≥150 ml/kg/day for 48 hours
* No longer on parenteral nutrition.

Exclusion Criteria Phase 2

* Infants where there is a concern about mother's supply of breast milk being insufficient to meet demands (where donor milk is not being used to make up any shortfall);
* Known congenital metabolic disorder;
* Infant formula fed;
* Bilateral grade III or IV intraventricular haemorrhage;
* Any infant who has had gastrointestinal tract surgery;
* Refusal of consent;
* Refusal for the use of breast milk fortifier
* Birthweight \<1 kg

Primary outcomes:
measure: Phase 1: Accuracy of the Preemie system against reference laboratory International Standards Organization (ISO) methods.
timeFrame: 6 months
measure: Phase 1: Precision of the Preemie system against reference laboratory ISO methods.
timeFrame: 6 months
measure: Phase 2: Feasibility of recruiting infants to a study using Preemie system and associated NutriNTrack software to provide targeted individualised breast milk fortification in line with European recommendations.
timeFrame: 1 year
measure: Phase 2: Feasibility of using Preemie system and associated NutriNTrack software to provide targeted individualised breast milk fortification in line with European recommendations.
timeFrame: 1 year
Secondary outcomes:
measure: Phase 2: Enteral macronutrient intakes
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Enteral trace element intakes
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Enteral fat-soluble vitamin intakes
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Enteral wate-soluble vitamin intakes
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Enteral electrolyte intakes
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Feed intolerance
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Neonatal morbidities
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Ease of use of Preemie device
timeFrame: 1 year (end of study)
measure: Phase 2: Weight Gain
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Head Growth
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Length Growth
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Urea as a serum marker of nutritional status
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Albumin as a serum marker of nutritional status
timeFrame: 36 weeks corrected gestational age
measure: Phase 2: Alkaline Phosphatase (ALP) as a serum marker of nutritional status
timeFrame: 36 weeks corrected gestational age
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Mark J Johnson, PhD
role: PRINCIPAL_INVESTIGATOR
References: