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

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

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.

Study Overview

• Status: Completed
• Conditions: Weight Gain
• Intervention / Treatment: Combination product: Protein fortifier

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69004
    • Hôpital de la Croix Rousse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Weight-driven protein fortification; Individualized protein fortification based on weight gain	Combination product: Protein fortifier; Protein Fortifier to be added to Fortified human milk according to feeding regimen
EXPERIMENTAL: BUN-driven protein fortification; Individualized protein fortification based on BUN concentrations	Combination product: Protein fortifier; Protein Fortifier to be added to Fortified human milk according to feeding regimen

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Nestlé

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 9, 2017
• Primary Completion (ACTUAL): February 10, 2020
• Study Completion (ACTUAL): February 10, 2020

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (ACTUAL): July 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 5, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: 13.01.INF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No