SURF, Neurodevelopment, Growth Study in SGA Infants

Neurodevelopment, Growth, and Metabolic Syndrome Biomarkers in Term Small-for-gestational-age Infants Fed Standard or Nutrient-enriched Formula

The purpose of this study is to determine whether term SGA infants who are fed a nutrient-enriched pre-term formula will have a higher cognitive score, a more appropriate length-for-age Z-score (leading to a lower prevalence of Stunting) but higher blood pressure at 2 years of age compared to term SGA infants who are fed on a regular starter formula.

Study Overview

• Status: Withdrawn
• Conditions: Infant, Small for Gestational Age
• Intervention / Treatment: Other: Standard Formula; Other: Nutrient-enriched Formula

Detailed Description

This is multi-sites, interventional, double-blinded, randomized, 2-arm parallel-group clinical trial. Two HM fed groups will be included as comparator group.

The primary objectives are:

1. To evaluate neurodevelopment at 2 years of age in term small-for-gestational age (SGA) infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each human milk (HM)-fed group.
2. To evaluate length-for-age Z-score at 2 years of age in term SGA infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each HM-fed group.
3. To evaluate systolic blood pressure at 2 years of age in term SGA infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each HM-fed group.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Having obtained his/her parents' (or his/her legally accepted representative's LAR's]) written informed consent and having evidence of a personally signed and dated informed consent document indicating that the infant's parents/LAR have been informed of pertinent aspects of the study.
2. For infants in formula fed groups only: infants who require formula feeding due to lactation failure after minimum 2 rounds of breastfeeding counselling.
3. Birth Weight < 10th percentile at term using the 2013 INTERGROWTH-21st Growth Charts for girls and boys.
4. Full term birth (gestational age ≥ 37 weeks and ≤ 41 weeks + 6 days), with gestational age estimated using fetal anthropometry by ultrasonography in early 1st trimester of pregnancy or calculated using the first day of the last menstrual period + 40 weeks if fetal anthropometry data for term calculation is not available or was collected after the 1st trimester.
5. Age <45 days at time of enrollment
6. For infants in the HM-fed AGA comparator group only: born to mothers with pre-pregnancy body mass index (BMI) ≥ 18.5 and <25kg/m2

Exclusion Criteria:

1. mothers with Type-1 Diabetes
2. mothers who smoked >10 cigarettes per day during pregnancy.
3. mothers who used Illicit drugs (e.g. marijuana, cocaine, amphetamines, or heroin) or alcohol (>3 alcoholic beverages per week) during pregnancy
4. Suspected or documented systemic or congenital infections (e.g Human Immunodeficiency virus, cytomegalovirus)
5. Genetic or any other type of congenital malformations, metabolic, cardiovascular, gastrointestinal, pancreatic or hepatic diseases or medical conditions that could compromise growth and/or food intake.
6. Fit to be discharged from neonatal intensive care unit (NICU) in > 5 consecutive days with the exception of infants in the NICU due to jaundice only.
7. Known or suspected intolerance/ allergy to milk protein or any ingredient in the study formulas
8. For infants in the HM-fed groups only: infants who are consuming fortified human milk or formula.
9. Participation in any other interventional clinical trial during the 14 days prior to enrollment.
10. Infants or infant's family who in the investigator's judgement cannot be expected to comply with the protocol or study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Randomized Standard Formula-fed; Product will be given to the formula-fed groups during the intervention phase of the study (enrollment to age 6 months).	Other: Standard Formula; Standard Formula
EXPERIMENTAL: Randomized Nutrient-enriched formula-fed; Product will be given to the formula-fed groups during the intervention phase of the study (enrollment to age 6 months).	Other: Nutrient-enriched Formula; Nutrient-enriched Formula
NO_INTERVENTION: Non-randomized HM-fed; Infants in HM-fed group will be fed through 6 months of age, along with micronutrient supplementation per routine clinical practice.
NO_INTERVENTION: Non-Randomized HM-fed; Infants in HM-fed group will be fed through 6 months of age, along with micronutrient supplementation per routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of neurodevelopment	Assessed using Bayley Scales of Infant and Toddler Development® - Third Edition - (To compare with the standard Bayley scores).	at the baseline (2 years of age)
Evaluation of length-for-age Z-score	Using the WHO growth chart	Evaluated once at 2 years of age
Systolic Blood pressure	Systolic and diastolic blood pressure measurement from 1 to 6 months of age	at baseline (2 years of age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of insulin sensitivity	HOMA-IR (Homeostatic Model Assessment - Insulin Resistance) calculated from Basal (Fasting) plasma glucose and insulin concentrations.	at Baseline ( 2 years of age).
Evaluation of insulin sensitivity	HOMA-IR (Homeostatic Model Assessment - Insulin Resistance) calculated from Basal (Fasting) plasma glucose and insulin concentrations.	at last visit ( 5 years of age).
Neurodevelopment	Assessed using Wechsler Preschool and Primary Scale of Intelligence™ - Fourth Edition (WPPSI-IV) - (to compare the scores against the standard scores).	At last visit ( 5 years of age)
Safety (Adverse Event reporting)	Assessed by Type, incidence, severity, seriousness and relationship to study formulas of AEs (including Infection) among the study subjects.	From 1 to 6 months of age & 6 months to 5 years of age.
Growth (Length)	Evaluation of length-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(<2.5th percentile indicating prevalence of stunting).	At 2 years of age
Growth (Weight)	Evaluation of weight-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(<2.5th percentile indicating prevalence of stunting).	At 2 years of age
Growth (Head circumference)	Evaluation of head circumference-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(<2.5th percentile indicating prevalence of stunting).	At 2 years of age
Growth (Z-Scores)	Evaluation of weight-for-length Z-scores in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(<2.5th percentile indicating prevalence of stunting).	At 2 years of age
Evaluation of serum markers of bone metabolism	Assessed by Incidence of abnormal serum (Calcium, phosphorus, Alkaline phosphatase).	At visit 1 (<44 days)
Evaluation of serum markers of bone metabolism	Assessed by Incidence of abnormal serum (Calcium, phosphorus, Alkaline phosphatase).	At visit 4 (6 months)
Evaluation of urinary markers of bone metabolism	Assessed by Incidence of urine biochemistries (calcium, phosphorous).	At visit 1 (<44 days)
Evaluation of urinary markers of bone metabolism	Assessed by Incidence of urine biochemistries (calcium, phosphorous).	At visit 4 (6 months)
Body fat mass (%)	Assessed by Deterium dilution	evaluated until 5 years of age.

Collaborators and Investigators

• Sponsor: Nestlé

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 31, 2017
• Primary Completion (ANTICIPATED): June 2, 2017
• Study Completion (ANTICIPATED): June 2, 2017

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (ACTUAL): April 24, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 14.11.INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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