Prematurity; ExtremeNCT04325308
Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk
A study testing Protein-enriched human milk diet and Usual human milk diet in people with Prematurity; Extreme and Feeding Disorder Neonatal, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 4 days
- Conditions the study is for
- Prematurity; Extreme, Feeding Disorder Neonatal, Breast Milk Expression
- What is being tested?
- Protein-enriched human milk diet and Usual human milk diet
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2020to 30 Sep 2027
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 4 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age ≤ 28 weeks of gestation
- Postnatal age < 96 hours
Who cannot join
- Congenital malformations
- Chromosomal anomalies
- Terminal illness needing to limit or withhold support
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35233
About this study
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
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.
Read the 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.
- Conditions
- Prematurity; Extreme, Feeding Disorder Neonatal, Breast Milk Expression, Growth Failure, Microbial Colonization
- Being tested
- Protein-enriched human milk diet, Usual human milk diet
- Medical subject headings
- Premature Birth, Breast Milk Expression, Failure to Thrive, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein-enriched human milk dietProcedure or surgery
1.2 g of human-based protein will be added to each 100 ml of human milk administered
Usual human milk dietProcedure or surgery
Human-based protein will not be added to the human milk administered.
| Study group | Role | What they receive |
|---|---|---|
| Protein-enriched human milk diet | Experimental | Infants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. Receives: Procedure: Protein-enriched human milk diet |
| Usual human milk diet | Active comparator | Infants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. Receives: Procedure: Usual human milk diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fat-free Mass(FFM)-For-age Z-score
Estimated by air displacement plethysmography. FFM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.
Measured: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Secondary outcomes (13)
Fat Mass(FM)-For-age Z-score
Estimated by air displacement plethysmography. FM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.
Measured: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Body Fat(BF)-For-age Z-score
Body fat estimated by air displacement plethysmography. BF measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.
Measured: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Anthropometric Measurements
Weight, length, and head circumference measurements. Measurements were converted into Z-scores based on Fenton growth curves (2013). They were calculated at birth and at 36 weeks. This outcome represents the change in weight, length, and head circumference Z-score during the course of the study (i.e., the Z-score at birth was subtracted from the Z-score at 36 weeks).
A value of 0 represents that the infant's Z-score is the same at the beginning and the end of the study. Positive values indicate the increase in the infant's Z-score during the study; negative values indicate the decrease in the infant's Z-score during the study.
Measured: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Growth Rate
Weight gain in g/kg/day
Measured: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Number of Participants With Postnatal Growth Failure
Diagnosis of growth failure (weight < 10th percentile using the 2013 Fenton growth curves)
Measured: 36 weeks or hospital discharge (whichever occurred first)
Number of Participants With Diagnosis of Necrotizing Enterocolitis
Diagnosis of necrotizing enterocolitis stage 2 or 3
Measured: From birth up to 120 days following birth
Number of Participants With Diagnosis of Intestinal Perforation
Diagnosis of intestinal perforation
Measured: From birth up to 120 days following birth
Death
Death prior to 121 days of life
Measured: Birth to 120 days
Culture-proven Sepsis
Diagnosis of sepsis with positive blood cultures
Measured: Birth to 120 days
Number of Days Alive and Receiving Full Enteral Feeding
Time to full enteral feeding days
Measured: Birth to 28 days
Number of Episodes of Feeding Intolerance
Interruption or cessation of enteral feeds for a period greater than 12 hours for abnormal abdominal examination
Measured: Birth to 28 days
Duration of Hospital Stay in Days
From day of admission to day of hospital discharge to home
Measured: Birth to 120 days or discharge, whichever occurs first
Serum BUN
Highest serum BUN value in the first 28 days after birth
Measured: Birth to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start13 Aug 2020
- Primary completion2 Jan 2023
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prematurity; ExtremeStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Ariel A. Salas, University of Alabama at Birmingham
- Investigators
- Ariel Salas, MD, MSPH, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325308
- Sponsor's protocol ID
- IRB-300005089
- Other IDs
- K23HD102554
- Status last verified
- Aug 2026
- First submitted
- 25 Mar 2020
- Last updated
- 21 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tucker MJ, Jeffcoat SH, Argent T, Travers CP, Salas AA. Severity of Bronchopulmonary Dysplasia in Infants Born Extremely Preterm and Randomized to Early Human Milk Fortification with a Donor Milk-Derived Fortifier for 2 Weeks. J Pediatr. 2025 Dec;287:114750. doi: 10.1016/j.jpeds.2025.114750. Epub 2025 Jul 24.
PubMed 40714049Salas AA, Gunawan E, Nguyen K, Reeves A, Argent V, Finck A, Carlo WA. Early Human Milk Fortification in Infants Born Extremely Preterm: A Randomized Trial. Pediatrics. 2023 Sep 1;152(3):e2023061603. doi: 10.1542/peds.2023-061603.
PubMed 37551512
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04325308
- Acronym / sponsor ID
- IRB-300005089
- Conditions
- Prematurity; Extreme, Feeding Disorder Neonatal, Breast Milk Expression, Growth Failure, Microbial Colonization
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 13 Aug 2020 (actual)
- Primary completion
- 2 Jan 2023 (actual)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 27 Mar 2020 (actual)
- Results
- Posted 13 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protein-enriched human milk diet | Experimental | Procedure: Protein-enriched human milk dietInfants in this group will receive protein-enriched expressed human milk or donor human milk during the first 2 weeks after birth. |
| Usual human milk diet | Active comparator | Procedure: Usual human milk dietInfants in this group will receive either expressed human milk or donor human milk during the first 2 weeks after birth. |
Who may qualify
- Ages
- 1 day to 4 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Gestational age ≤ 28 weeks of gestation
- Postnatal age < 96 hours
Key exclusion criteria (3 listed)
- Congenital malformations
- Chromosomal anomalies
- Terminal illness needing to limit or withhold support
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protein-enriched human milk diet1.2 g of human-based protein will be added to each 100 ml of human milk administered | Procedure or surgery | Protein-enriched human milk diet |
| Usual human milk dietHuman-based protein will not be added to the human milk administered. | Procedure or surgery | Usual human milk diet |
Primary outcome
Fat-free Mass(FFM)-For-age Z-score
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Estimated by air displacement plethysmography. FFM measurements were converted into Z-scores using updated, sex-specific reference curves of body composition in preterm infants (Norris et al, 2019). A Z-score of 0 represents the population mean. Z-score values closer to 0 represent a better outcome. No relevant thresholds have been defined.
13 secondary outcomes
Fat Mass(FM)-For-age Z-score
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Body Fat(BF)-For-age Z-score
Time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer
Anthropometric Measurements
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Growth Rate
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge (whichever occurred first)
Number of Participants With Postnatal Growth Failure
Time frame: 36 weeks or hospital discharge (whichever occurred first)
Number of Participants With Diagnosis of Necrotizing Enterocolitis
Time frame: From birth up to 120 days following birth
Number of Participants With Diagnosis of Intestinal Perforation
Time frame: From birth up to 120 days following birth
Death
Time frame: Birth to 120 days
Culture-proven Sepsis
Time frame: Birth to 120 days
Number of Days Alive and Receiving Full Enteral Feeding
Time frame: Birth to 28 days
Number of Episodes of Feeding Intolerance
Time frame: Birth to 28 days
Duration of Hospital Stay in Days
Time frame: Birth to 120 days or discharge, whichever occurs first
Serum BUN
Time frame: Birth to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40714049Tucker MJ, Jeffcoat SH, Argent T, Travers CP, Salas AA. Severity of Bronchopulmonary Dysplasia in Infants Born Extremely Preterm and Randomized to Early Human Milk Fortification with a Donor Milk-Derived Fortifier for 2 Weeks. J Pediatr. 2025 Dec;287:114750. doi: 10.1016/j.jpeds.2025.114750. Epub 2025 Jul 24.
- Results publication: PubMed 37551512Salas AA, Gunawan E, Nguyen K, Reeves A, Argent V, Finck A, Carlo WA. Early Human Milk Fortification in Infants Born Extremely Preterm: A Randomized Trial. Pediatrics. 2023 Sep 1;152(3):e2023061603. doi: 10.1542/peds.2023-061603.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ariel Salas, MD, MSPH principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protein-enriched human milk diet and Usual human milk diet in people with Prematurity; Extreme and Feeding Disorder Neonatal, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fat-free Mass(FFM)-For-age Z-score (time frame: 36 weeks or hospital discharge, up to 120 days following birth, whichever is longer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04325308, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.