Comparison of Two Dose Adjustment Strategies of a Human Milk Protein Fortifier in Preterm Infants

Study Overview
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Brief Summary
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The primary objective is to compare weight gain (g/day) of infants receiving new protein fortifier (PF) according to a blood urea nitrogen (BUN)-driven fortification regimen to weight gain (g/day) of infants receiving PF according to a weight-driven fortification regimen (standard of care) over a 21 day period.

Official Title
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Comparison of Two Regimens of Individualized, Adjustable Human Milk Fortification in Pretem Infants Using a New Modular Protein-only Fortifier

Conditions
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Weight Gain

Intervention / Treatment
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* Combination Product: Protein fortifier


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age in weeks: 23 weeks 0 days and 31 weeks 6 days. Birth weight less or equal to 1500 g Minimum enteral intake of 150-160 mL/kg/d fortified HM Parents, liable parent, or legal representative (LR) if applicable are willing and able to sign written informed consent and written informed consent is obtained prior to trial entry Exclusion Criteria: Infants with weight z-score < -2 SD, based on the Fenton growth chart (Fenton 2013) Intra-ventricular hemorrhage (grade 3-4) determined using cranial ultrasonography or periventricular leukomalacia. Renal disease determined by symptoms (oliguria, anuria, proteinuria, hematuria) associated with an increased creatinine. Cholestasis (total bilirubin > 5 mg/dL or 85 umol/L and direct bilirubin > 20% of total bilirubin) associated with one or more abnormal liver function tests (AST, ALT, or GGT). Major congenital malformations that may impact ability to accept enteral feedings (i.e., severe cleft palate, etc.). Suspected or documented systemic or congenital infections (i.e., human immunodeficiency virus, cytomegalovirus, etc.). Evidence of cardiac, respiratory, endocrinologic, hematologic, gastrointestinal, or other systemic diseases that may impact growth, e.g.,: NEC grade above or equal to 2 Uncontrolled sepsis Suspected or documented maternal substance abuse: Born to mothers who smoked > 10 cigarettes per day during pregnancy Born to mothers who used illicit drugs (e.g. marijuana, cocaine, amphetamines, or heroin) or alcohol (> 3 alcoholic beverages per week) during pregnancy Subjects' parent(s) or legal representative who are not willing and not able to comply with scheduled visits and the requirements of the study protocol Infants who have received any experimental treatment or received any other investigational intervention (procedure or product) unrelated to this trial, prior to enrollment

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Weight-driven protein fortification<br>Individualized protein fortification based on weight gain | Combination Product: Protein fortifier<br>* Protein Fortifier to be added to Fortified human milk according to feeding regimen<br>|
| Experimental: BUN-driven protein fortification<br>Individualized protein fortification based on BUN concentrations | Combination Product: Protein fortifier<br>* Protein Fortifier to be added to Fortified human milk according to feeding regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of weight gain | To compare weight gain (g/day) of infants receiving new protein fortifier (PF) according to a BUN-driven fortification regimen to weight gain (g/day) of infants receiving PF according to a weight-driven fortification regimen | From Day 6 to Day 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of weight gain (g/day) of infants after 1 and 3 weeks of individualized protein fortification to weight gain during the 5-day period of standard Human Milk (HM) fortification | Comparison of weight gain (g/day) of infants after 1 and 3 weeks of individualized protein fortification to weight gain during the 5-day period of standard HM fortification | Day 6 to Day 13, and Day 6 to Day 27 | 
| Changes in growth parameters: Lengths (crown-heel and knee-heel) and length gain (cm) | Changes in growth parameters: Lengths (crown-heel and knee-heel) and length gain (cm) | Day 6 to Day 27 (minimum) | 
| Changes in growth parameters: head circumference and head circumference gain (cm) | Changes in growth parameters: head circumference and head circumference gain (cm) | Day 6 to Day 27 (minimum) | 
| Changes in growth parameters: BMI and BMI changes (kg body weight/m^2) | Changes in growth parameters: BMI and BMI changes (kg body weight/m^2) | Day 6 to Day 27 (minimum) | 
| Body composition including lean fat mass and fat-free mass | Body composition including lean fat mass and fat-free mass | Day 6 to Day 27 (minimum) | 
| Weight at hospital discharge | Weight at hospital discharge | Day 27 (minimum) | 
| Macronutrient content in human milk | Macronutrient content in human milk using a Miris Human Milk Analyzer to measure the composition of the human milk | Day 6 to Day 27 (minimum) | 
| Feeding and gastrointestinal (GI) tolerance | Feeding and gastrointestinal (GI) tolerance determined using Digestive tolerance scores based on four binary parameters (0 = absence or 1 = presence) collected in daily routine care: Sore abdomen, liquid stools, gastric residuals, and regurgitation or vomiting | Day 6 to Day 27 (minimum) | 
| Safety evaluation including number of subjects with AEs | Safety evaluation including number of subjects with AEs | Day 1 to Day 27 (minimum) | 
| Biochemistry markers collected from blood and urine as part of routine NICU standard of care | Biochemistry markers collected from blood and urine as part of routine NICU standard of care: Routine biochemistries in Blood/Serum and Urine (in spot urine samples), and Nutrition markers in Blood/serum: albumin, pre-albumin, alkaline phosphatase, triglycerides and vitamin D | Day 6 to Day 27 (minimum) |