PrematurityENACT+NCT05525585
Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants
A study testing Early HMF and Delayed HMF in people with Prematurity and Light-For-Dates, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
In this proposed clinical trial, the investigators will randomize 80 very preterm (VPT) infants to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification and determine if providing early protein supplementation through early fortification results in higher FFM-for-age z scores and… Read more about this study
- Who is it for?
- Ages 1 day to 4 days
- Conditions the study is for
- Prematurity, Light-For-Dates, Enteral Feeding Intolerance
- What is being tested?
- Early HMF and Delayed HMF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2022to May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 29 to 33 weeks of gestation
- Birth weight < 1800 g
- Postnatal age < 96 hours
Who cannot join
- Small for gestational age (<5th percentile)
- Major congenital/chromosomal anomalies
- Terminal illness needing withhold or limit 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 Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants: a Randomized Clinical Trial
In this proposed clinical trial, the investigators will randomize 80 very preterm (VPT) infants to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification and determine if providing early protein supplementation through early fortification results in higher FFM-for-age z scores and more diversity in the gut microbiome.
- Conditions
- Prematurity, Light-For-Dates, Enteral Feeding Intolerance
- Being tested
- Early HMF, Delayed HMF
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early HMFDietary supplement
Mom's milk or donor milk will be fortified between postnatal day 4 and 7
Delayed HMFDietary supplement
Mom's milk or donor milk will be fortified between postnatal day 10 and 14
| Study group | Role | What they receive |
|---|---|---|
| Early human milk fortification (HMF) group | Experimental | A human milk fortifier will be added to the feeds between days 4 to 7, after a total feeding volume greater than 120 ml/kg/day is achieved. Receives: Dietary Supplement: Early HMF |
| Delayed human milk fortification (HMF) group | Active comparator | A human milk fortifier will be added to the feeds between days 10 to 14, after a total feeding volume greater than 120 ml/kg/day is achieved. Receives: Dietary Supplement: Delayed HMF |
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
Measured: Postnatal day 14 to 21
Secondary outcomes (10)
Fecal microbiome composition
Determined by 16S RNA sequencing of bacteria in stool samples
Measured: Birth to 36 weeks postmenstrual age
Growth - Weight
Measured weekly in grams and z scores as part of routine care
Measured: Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Length
Measured weekly in cm and z scores as part of routine care
Measured: Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Head circumference
Measured weekly in cm and z scores as part of routine care
Measured: Birth to 36 weeks postmenstrual age or hospital discharge
Growth rate
Weight gain in g/kg/day
Measured: Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with postnatal growth faltering
Diagnosis of growth faltering (decline in weight-for-age z score from birth to 36 weeks postmenstrual age greater than 1.2
Measured: Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with diagnosis of necrotizing enterocolitis
Diagnosis of necrotizing enterocolitis stage 2 or 3
Measured: Birth to 60 days or discharge
Number of participants with diagnosis of intestinal perforation
Diagnosis of intestinal perforation
Measured: Birth to 10 days
Death
Death prior to postnatal day 60
Measured: Birth to 60 days
Duration of hospital stay in days
From day of admission to day of hospital discharge to home
Measured: Birth to 60 days or discharge, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start17 Nov 2022
- Primary completion1 Nov 2023
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies 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
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Mead Johnson Nutrition
- Responsible party
- Principal investigator, Ariel A. Salas, University of Alabama at Birmingham
- Investigators
- Ariel A. Salas, MD, MSPH, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05525585
- Sponsor's protocol ID
- IRB-300009921
- Other IDs
- 000538159
- Acronym
- ENACT+
- Status last verified
- Jun 2026
- First submitted
- 29 Aug 2022
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Salas AA, Gunawan E, Jeffcoat S, Nguyen K. Early full enteral nutrition with fortified milk in very preterm infants: a randomized clinical trial. Am J Clin Nutr. 2025 May;121(5):1117-1123. doi: 10.1016/j.ajcnut.2025.02.019. Epub 2025 Feb 21.
PubMed 39986385
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Human Milk Fortification After Early, Exclusive, Enteral Nutrition in Very Preterm Infants: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05525585
- Acronym / sponsor ID
- ENACT+ / IRB-300009921
- Conditions
- Prematurity, Light-For-Dates, Enteral Feeding Intolerance
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Mead Johnson Nutrition
- Study start
- 17 Nov 2022 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- May 2027 (estimated)
- First posted
- 1 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this proposed clinical trial, the investigators will randomize 80 very preterm (VPT) infants to receive either early (between day 4 and 7) or delayed (between day 10 and 14) fortification and determine if providing early protein supplementation through early fortification results in higher FFM-for-age z scores and more diversity in the gut microbiome.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early human milk fortification (HMF) group | Experimental | Dietary Supplement: Early HMFA human milk fortifier will be added to the feeds between days 4 to 7, after a total feeding volume greater than 120 ml/kg/day is achieved. |
| Delayed human milk fortification (HMF) group | Active comparator | Dietary Supplement: Delayed HMFA human milk fortifier will be added to the feeds between days 10 to 14, after a total feeding volume greater than 120 ml/kg/day is achieved. |
Who may qualify
- Ages
- 1 day to 4 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Gestational age 29 to 33 weeks of gestation
- Birth weight < 1800 g
- Postnatal age < 96 hours
Key exclusion criteria (3 listed)
- Small for gestational age (<5th percentile)
- Major congenital/chromosomal anomalies
- Terminal illness needing withhold or limit 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 |
|---|---|---|
| Early HMFMom's milk or donor milk will be fortified between postnatal day 4 and 7 | Dietary supplement | Early human milk fortification (HMF) group |
| Delayed HMFMom's milk or donor milk will be fortified between postnatal day 10 and 14 | Dietary supplement | Delayed human milk fortification (HMF) group |
Primary outcome
Fat-free mass(FFM)-for-age Z-score
Time frame: Postnatal day 14 to 21
Estimated by air displacement plethysmography
10 secondary outcomes
Fecal microbiome composition
Time frame: Birth to 36 weeks postmenstrual age
Growth - Weight
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Length
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge
Growth - Head circumference
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge
Growth rate
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with postnatal growth faltering
Time frame: Birth to 36 weeks postmenstrual age or hospital discharge
Number of participants with diagnosis of necrotizing enterocolitis
Time frame: Birth to 60 days or discharge
Number of participants with diagnosis of intestinal perforation
Time frame: Birth to 10 days
Death
Time frame: Birth to 60 days
Duration of hospital stay in days
Time frame: Birth to 60 days or discharge, whichever occurs first
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Results publication: PubMed 39986385Salas AA, Gunawan E, Jeffcoat S, Nguyen K. Early full enteral nutrition with fortified milk in very preterm infants: a randomized clinical trial. Am J Clin Nutr. 2025 May;121(5):1117-1123. doi: 10.1016/j.ajcnut.2025.02.019. Epub 2025 Feb 21.
- Individual participant dataSharing planned: Undecided
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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 A. 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 Early HMF and Delayed HMF in people with Prematurity and Light-For-Dates, 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 3 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 15 Jun 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?
This study is still under way. Results are not available in the source record yet.
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: Postnatal day 14 to 21). 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 NCT05525585, which also lists 1 linked publication.
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 15 Jun 2026.