Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk

• ClinicalTrials.gov Identifier: NCT04325308
• Recruitment Status: Active, not recruiting
• First Posted: March 27, 2020
• Last Update Posted: January 25, 2023
• Sponsor: University of Alabama at Birmingham
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Ariel A. Salas, University of Alabama at Birmingham

Study Description

Brief Summary:

The central hypothesis of this clinical trial is that, in extremely preterm infants, protein-enriched human milk diets compared to usual human milk diets during the first 2 weeks after birth increase fat-free mass (FFM)-for-age Z scores and promote maturation of the gut microbiome at term corrected age.

Condition or disease	Intervention/treatment	Phase
Prematurity; Extreme; Feeding Disorder Neonatal; Breast Milk Expression; Growth Failure; Microbial Colonization	Procedure: Protein-enriched human milk diet; Procedure: Usual human milk diet	Not Applicable

Detailed Description:

Masked randomized clinical trial in which extremely preterm infants fed human milk will be randomly assigned to receive either a protein-enriched diet (intervention group) or a usual diet (control group) within the first 96 hours after birth.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Caregivers and primary outcome evaluators will be masked. Nutrition room staff not involved in patient care will be responsible for determining participant allocation to one of the supplementation groups by opening sequentially numbered sealed envelopes, dispensing feeding syringes with the allocated human milk diet (protein-enriched or usual), and masking caregivers administering the assigned dietary intervention.
• Primary Purpose: Prevention
• Official Title: Early Life Protein-enriched Human Milk Diets to Increase Lean Body Mass Accretion and Diversity of the Gut Microbiome in Extremely Preterm Infants: a Randomized Trial
• Actual Study Start Date: August 13, 2020
• Actual Primary Completion Date: January 2, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Protein-enriched human milk diet; Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth.	Procedure: Protein-enriched human milk diet; 1.2 g of human-based protein will be added to each 100 ml of human milk administered
Active Comparator: Usual human milk diet; Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth.	Procedure: Usual human milk diet; Human-based protein will not be added to the human milk administered.

Outcome Measures

Primary Outcome Measures :

1. Fat-free mass(FFM)-for-age Z-score [ Time Frame: 36 weeks or hospital discharge ]
   FFM accretion will be estimated by air displacement plethysmography

Secondary Outcome Measures :

1. Fat mass(FM)-for-age Z-score [ Time Frame: 36 weeks or hospital discharge ]
   FM accretion will be estimated by air displacement plethysmography
2. Body fat(BF)-for-age Z-score [ Time Frame: 36 weeks or hospital discharge ]
   Percent BF will be estimated by air displacement plethysmography
3. Anthropometric measurements [ Time Frame: Birth to 36 weeks postmenstrual age or hospital discharge ]
   Weight, length, and head circumference measurements at regular intervals
4. Growth rate [ Time Frame: Birth to 36 weeks postmenstrual age or hospital discharge ]
   Weight gain in g/kg/day
5. Number of participants with postnatal growth failure [ Time Frame: 36 weeks or hospital discharge ]
   Diagnosis of growth failure (weight < 10th percentile)
6. Number of participants with diagnosis of necrotizing enterocolitis [ Time Frame: Birth to 120 days or discharge, whichever occurs first ]
   Diagnosis of necrotizing enterocolitis stage 2 or 3
7. Number of participants with diagnosis of intestinal perforation [ Time Frame: Birth to 120 days or discharge, whichever occurs first ]
   Diagnosis of intestinal perforation
8. Death [ Time Frame: Birth to 120 days ]
   Death prior to 121 days of birth
9. Culture-proven sepsis [ Time Frame: Birth to 120 days ]
   Diagnosis of sepsis with positive blood cultures
10. Number of days alive and receiving full enteral feeding [ Time Frame: Birth to 28 days ]
    Total number of full enteral feeding days
11. Number of episodes of feeding intolerance [ Time Frame: Birth to 28 days ]
    Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination
12. Duration of hospital stay in days [ Time Frame: Birth to 120 days or discharge, whichever occurs first ]
    From day of admission to day of hospital discharge to home
13. Serum creatinine [ Time Frame: Birth to 28 days ]
    Highest serum creatinine value in the first 28 days after birth

Other Outcome Measures:

1. Changes in intestinal microbiome [ Time Frame: Birth to 36 weeks postmenstrual age ]
   Determined by molecular analyses of fecal samples
2. Cognitive outcomes [ Time Frame: 2 years of corrected age ]
   Determined by Bayley assessment

Eligibility Criteria

• Ages Eligible for Study: 1 Day to 4 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Gestational age ≤ 28 weeks of gestation
• Postnatal age < 96 hours

Exclusion Criteria:

• Congenital malformations
• Chromosomal anomalies
• Terminal illness needing to limit or withhold support

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

Sponsors and Collaborators

University of Alabama at Birmingham

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Ariel Salas, MD, MSPH; University of Alabama at Birmingham

More Information

• Responsible Party: Ariel A. Salas, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT04325308
• Other Study ID Numbers: 300005089; K23HD102554 ( U.S. NIH Grant/Contract )
• First Posted: March 27, 2020
• Last Update Posted: January 25, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Communicable Diseases; Infections; Failure to Thrive; Feeding and Eating Disorders; Disease Attributes; Pathologic Processes; Mental Disorders