Very Preterm Maturity of InfantTHRIVENCT06266455
Individualized Nutrition to Optimize Preterm Infant Growth and Neurodevelopment
A study testing Standardized Fortification and Adjustable Fortification in people with Very Preterm Maturity of Infant and Very Low Birth Weight Infant, run by Children's National Research Institute at 1 site in United States.
Trial summary
Human milk has several well-established benefits but does not adequately meet the increased nutritional demands of the growing preterm infant, necessitating additional nutrient supplementation in a process known as fortification. In U.S. Read more about this study
- Who is it for?
- Ages Up to 4 weeks
- Conditions the study is for
- Very Preterm Maturity of Infant, Very Low Birth Weight Infant
- What is being tested?
- Standardized Fortification and Adjustable Fortification
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2024to Jan 2034
- 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 Up to 4 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Birth gestational age (GA) of ≤32 weeks
- Postnatal age ≤4 weeks at time of enrollment
- Maternal plan to provide human milk to infant, and consent to providing donor human milk if insufficient maternal milk supply
- Maternal age > 18 years old
Who cannot join
- Formula feeding prior to 36 weeks PMA or discharge home (whichever achieved first), either secondary to parental preference or medical necessity
- Dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorder, chromosomal abnormality, or congenital infection
- Dysgenetic or major destructive brain lesions detected by head ultrasound before enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's National Hospital
Washington D.C., District of Columbia, 20010
Catherine Limperopoulos, Ph.D., 202-476-5293, CLimpero@childrensnational.org
Katherine M. Ottolini, M.D., 202-476-8905, KOttolin@childrensnational.org
About this study
Official title: Transforming Health and Resilience Via Individualized Nutrition in Very Preterm Infants for Extrauterine Growth and Development
Human milk has several well-established benefits but does not adequately meet the increased nutritional demands of the growing preterm infant, necessitating additional nutrient supplementation in a process known as fortification. In U.S. neonatal intensive care units (NICUs), human milk is primarily supplemented using standardized fortification, in which a multicomponent fortifier is added to human milk to achieve assumed nutrient content based on standard milk reference values. However, this method does not account for the significant variability in human milk composition or in preterm infant metabolism, and up to half of all very premature infants experience poor growth and malnutrition using current nutritional practices. Poor postnatal growth has adverse implications for the developing preterm brain and long-term neurodevelopment.
Recent advances allow for individualized methods of human milk fortification, including adjustable and targeted fortification. Adjustable fortification uses laboratory markers of protein metabolism (BUN level) to estimate an infant's protein requirements. In targeted fortification, a milk sample is analyzed to determine its specific macronutrient and energy content, with additional macronutrient supplementation provided as needed to achieve goal values. Emerging data suggest that both methods are safe and effective for improving growth, however information on their comparable efficacy and neurodevelopmental implications are lacking, particularly using advanced quantitative brain MRI (qMRI) techniques.
Through this prospective, randomized-controlled trial, the investigators will compare the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants. Infants will be randomized to receive one of three nutritional interventions: standardized (control group), adjustable, or targeted human milk fortification. Infants will undergo their assigned nutritional intervention until term-equivalent age or discharge home, whichever is achieved first. Brain qMRI will be performed at term-corrected age, and neurodevelopmental follow-up will be performed through 5 years of age.
- Being tested
- Standardized Fortification, Adjustable Fortification
- Keywords
- Magnetic Resonance Imaging, Neurodevelopment, Nutrition, Fortification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized FortificationDietary supplement
Fortification with liquid, bovine-based HMF to assumed human milk content of 24kcal/oz
Adjustable FortificationDietary supplement
Additional liquid protein supplementation to maintain serum BUN levels within goal range (9-14mmol/dL)
Adjustable FortificationDietary supplement
Additional liquid protein and/or MCT oil supplementation to maintain protein, fat, and energy intake within goal range based upon mid-infrared human milk analysis
| Study group | Role | What they receive |
|---|---|---|
| Standardized Fortification | Active comparator | All study participants will undergo feed advancement and fortification with liquid, bovine-based human milk fortifier (HMF) to an assumed human milk content of 24kcal/oz per the Children's National Hospital NICU standardized clinical feeding protocol. The same milk fortification recipes are utilized for mother's own milk (MOM) and donor human milk (DHM). Each infant's growth trajectory is monitored (weight, length, and head circumference) with dietary modifications performed as needed based on growth parameters.
Growth failure is defined as a decline in weight-for-age z-score by greater than 1 standard deviation (>1 SD) beginning 1 week after reaching goal fortified feeds. For infants who demonstrate growth failure, Step 1 will be to add medium chain triglyceride (MCT) oil. If growth remains sub-optimal, Step 2 will be to add liquid protein. Receives: Dietary Supplement: Standardized Fortification |
| Adjustable | Experimental | Adjustable fortification will begin 1 week after tolerating goal feeds of standardized fortification. Blood urea nitrogen (BUN) level as a marker of protein metabolism will be measured weekly, and supplementation with liquid protein will be adjusted as necessary to maintain a goal BUN level between 9-14mmol/dL, up to a maximum assumed protein intake of 4.5 g/kg/day. Liquid protein supplementation will be modified as follows:
* BUN Level <9 mmol/dL: Increase by 0.5g/kg/day
* BUN Level 9-14 mmol/dL: No change
* BUN Level >14 mmol/dL: Decrease by 0.25g/kg/day
* BUN Level >20 mmol/dL: Hold for 1 week and re-assess
Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after achieving BUN within goal range from adjustable fortification. For infants who demonstrate growth failure, MCT oil will be added and increased weekly as needed. Receives: Dietary Supplement: Standardized Fortification; Dietary Supplement: Adjustable Fortification |
| Targeted | Experimental | Targeted fortification will begin 1 week after tolerating goal feeds of standardized fortification. Additional supplementation with liquid protein and/or MCT oil will be provided based on twice weekly milk analysis using a mid-infrared human milk analyzer in order to meet macronutrient (carbohydrate, protein, lipid) and energy intake goals per pediatric nutrition guidelines (protein 4-4.5g/kg/day, fat 6-8g/kg/day, energy 120-130kcal/kg/day).
Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after receiving macronutrient and energy intake within goal range from targeted fortification. For infants with growth failure, total energy intake will be increased with additional protein and/or MCT oil supplementation. Energy intake may be increased weekly as needed. Receives: Dietary Supplement: Standardized Fortification; Dietary Supplement: Adjustable Fortification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight Gain Velocity
Weight gain velocity (grams per kilogram per day)
Measured: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Length Growth Velocity
Length growth velocity (centimeters per week)
Measured: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Head Circumference Growth Velocity
Head circumference growth velocity (centimeters per week)
Measured: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Total and Regional Brain Volumes
Total and regional (cortical and deep gray matter, white matter, amygdala-hippocampus, brainstem, cerebellum) brain volumes by MRI
Measured: Term-equivalent age (38 to 41 weeks postmenstrual age)
Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Summary scores in 13 different domains (habituation, attention, handling, self-regulation, arousal, excitability, lethargy, hypertonicity, hypotonicity, non-optimal reflex, asymmetric reflex, quality of movement, stress)
Measured: Term-equivalent age (38 to 41 weeks postmenstrual age)
Mullen Scales of Early Learning (MSEL)
Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score of 50 with standard deviation of 10)
Measured: 18 months corrected age
Mullen Scales of Early Learning (MSEL)
Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score score of 50 with standard deviation of 10)
Measured: 36 months (3 years) of age
Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)
Five primary indices: verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed (higher score indicates better performance, score range 40 to 160)
Measured: 60 months (5 years) of age
Differential Abilities Scale (2nd edition)-(DAS-II)
*For children with significant delays who may be unable to reach basal scores on the WPPSI-IV
Early years core battery: verbal, nonverbal, and spatial reasoning subtests (higher score indicates better performance, score range 40-170)
Measured: 60 months (5 years) of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start8 Feb 2024
- Primary completionJan 2034 (estimated)
- Study completionJan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Very Preterm Maturity of InfantStudies of the same condition, open and under way.
- More trials run by Children's National Research InstituteThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized-controlled trial comparing the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants randomized to receive one of three nutritional interventions: standardized (control), adjustable, or targeted human milk fortification.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06266455
- Sponsor's protocol ID
- Pro00000615
- Acronym
- THRIVE
- Status last verified
- Jul 2025
- First submitted
- 25 Sep 2023
- Last updated
- 11 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transforming Health and Resilience Via Individualized Nutrition in Very Preterm Infants for Extrauterine Growth and Development
- ClinicalTrials.gov ID
- NCT06266455
- Acronym / sponsor ID
- THRIVE / Pro00000615
- Keywords
- Magnetic Resonance Imaging, Neurodevelopment, Nutrition, Fortification
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Study start
- 8 Feb 2024 (actual)
- Primary completion
- Jan 2034 (estimated)
- Study completion
- Jan 2034 (estimated)
- First posted
- 20 Feb 2024 (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.
Human milk has several well-established benefits but does not adequately meet the increased nutritional demands of the growing preterm infant, necessitating additional nutrient supplementation in a process known as fortification. In U.S. neonatal intensive care units (NICUs), human milk is primarily supplemented using standardized fortification, in which a multicomponent fortifier is added to human milk to achieve assumed nutrient content based on standard milk reference values. However, this method does not account for the significant variability in human milk composition or in preterm infant metabolism, and up to half of all very premature infants experience poor growth and malnutrition using current nutritional practices. Poor postnatal growth has adverse implications for the developing preterm brain and long-term neurodevelopment.
Recent advances allow for individualized methods of human milk fortification, including adjustable and targeted fortification. Adjustable fortification uses laboratory markers of protein metabolism (BUN level) to estimate an infant's protein requirements. In targeted fortification, a milk sample is analyzed to determine its specific macronutrient and energy content, with additional macronutrient supplementation provided as needed to achieve goal values. Emerging data suggest that both methods are safe and effective for improving growth, however information on their comparable efficacy and neurodevelopmental implications are lacking, particularly using advanced quantitative brain MRI (qMRI) techniques.
Through this prospective, randomized-controlled trial, the investigators will compare the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants. Infants will be randomized to receive one of three nutritional interventions: standardized (control group), adjustable, or targeted human milk fortification. Infants will undergo their assigned nutritional intervention until term-equivalent age or discharge home, whichever is achieved first. Brain qMRI will be performed at term-corrected age, and neurodevelopmental follow-up will be performed through 5 years of age.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- Prospective, randomized-controlled trial comparing the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants randomized to receive one of three nutritional interventions: standardized (control), adjustable, or targeted human milk fortification.
| Arm | Type | Receives |
|---|---|---|
| Standardized Fortification | Active comparator | Dietary Supplement: Standardized FortificationAll study participants will undergo feed advancement and fortification with liquid, bovine-based human milk fortifier (HMF) to an assumed human milk content of 24kcal/oz per the Children's National Hospital NICU standardized clinical feeding protocol. The same milk fortification recipes are utilized for mother's own milk (MOM) and donor human milk (DHM). Each infant's growth trajectory is monitored (weight, length, and head circumference) with dietary modifications performed as needed based on growth parameters. Growth failure is defined as a decline in weight-for-age z-score by greater than 1 standard deviation (>1 SD) beginning 1 week after reaching goal fortified feeds. For infants who demonstrate growth failure, Step 1 will be to add medium chain triglyceride (MCT) oil. If growth remains sub-optimal, Step 2 will be to add liquid protein. |
| Adjustable | Experimental | Dietary Supplement: Standardized Fortification, Dietary Supplement: Adjustable FortificationAdjustable fortification will begin 1 week after tolerating goal feeds of standardized fortification. Blood urea nitrogen (BUN) level as a marker of protein metabolism will be measured weekly, and supplementation with liquid protein will be adjusted as necessary to maintain a goal BUN level between 9-14mmol/dL, up to a maximum assumed protein intake of 4.5 g/kg/day. Liquid protein supplementation will be modified as follows: * BUN Level <9 mmol/dL: Increase by 0.5g/kg/day * BUN Level 9-14 mmol/dL: No change * BUN Level >14 mmol/dL: Decrease by 0.25g/kg/day * BUN Level >20 mmol/dL: Hold for 1 week and re-assess Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after achieving BUN within goal range from adjustable fortification. For infants who demonstrate growth failure, MCT oil will be added and increased weekly as needed. |
| Targeted | Experimental | Dietary Supplement: Standardized Fortification, Dietary Supplement: Adjustable FortificationTargeted fortification will begin 1 week after tolerating goal feeds of standardized fortification. Additional supplementation with liquid protein and/or MCT oil will be provided based on twice weekly milk analysis using a mid-infrared human milk analyzer in order to meet macronutrient (carbohydrate, protein, lipid) and energy intake goals per pediatric nutrition guidelines (protein 4-4.5g/kg/day, fat 6-8g/kg/day, energy 120-130kcal/kg/day). Growth failure is defined as a decline in weight-for-age z-score by >1 SD beginning 1 week after receiving macronutrient and energy intake within goal range from targeted fortification. For infants with growth failure, total energy intake will be increased with additional protein and/or MCT oil supplementation. Energy intake may be increased weekly as needed. |
Who may qualify
- Ages
- Up to 4 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Birth gestational age (GA) of ≤32 weeks
- Postnatal age ≤4 weeks at time of enrollment
- Maternal plan to provide human milk to infant, and consent to providing donor human milk if insufficient maternal milk supply
- Maternal age > 18 years old
Key exclusion criteria (3 listed)
- Formula feeding prior to 36 weeks PMA or discharge home (whichever achieved first), either secondary to parental preference or medical necessity
- Dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorder, chromosomal abnormality, or congenital infection
- Dysgenetic or major destructive brain lesions detected by head ultrasound before enrollment
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 |
|---|---|---|
| Standardized FortificationFortification with liquid, bovine-based HMF to assumed human milk content of 24kcal/oz | Dietary supplement | Adjustable, Standardized Fortification, Targeted |
| Adjustable FortificationAdditional liquid protein supplementation to maintain serum BUN levels within goal range (9-14mmol/dL) | Dietary supplement | Adjustable |
| Adjustable FortificationAdditional liquid protein and/or MCT oil supplementation to maintain protein, fat, and energy intake within goal range based upon mid-infrared human milk analysis | Dietary supplement | Targeted |
Primary outcome
Weight Gain Velocity
Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Weight gain velocity (grams per kilogram per day)
Length Growth Velocity
Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Length growth velocity (centimeters per week)
Head Circumference Growth Velocity
Time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Head circumference growth velocity (centimeters per week)
Total and Regional Brain Volumes
Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)
Total and regional (cortical and deep gray matter, white matter, amygdala-hippocampus, brainstem, cerebellum) brain volumes by MRI
Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
Time frame: Term-equivalent age (38 to 41 weeks postmenstrual age)
Summary scores in 13 different domains (habituation, attention, handling, self-regulation, arousal, excitability, lethargy, hypertonicity, hypotonicity, non-optimal reflex, asymmetric reflex, quality of movement, stress)
Mullen Scales of Early Learning (MSEL)
Time frame: 18 months corrected age
Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score of 50 with standard deviation of 10)
Mullen Scales of Early Learning (MSEL)
Time frame: 36 months (3 years) of age
Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score score of 50 with standard deviation of 10)
Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)
Time frame: 60 months (5 years) of age
Five primary indices: verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed (higher score indicates better performance, score range 40 to 160)
Differential Abilities Scale (2nd edition)-(DAS-II)
Time frame: 60 months (5 years) of age
*For children with significant delays who may be unable to reach basal scores on the WPPSI-IV Early years core battery: verbal, nonverbal, and spatial reasoning subtests (higher score indicates better performance, score range 40-170)
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 11 Jul 2025.
- Individual participant dataSharing planned: No
Related trials for Very Preterm Maturity of Infant
RecruitingObservational study
Swiss Neonatal Network & Follow-up Group
Very Low Birth Weight Infant, Very Preterm Maturity of Infant
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standardized Fortification and Adjustable Fortification in people with Very Preterm Maturity of Infant and Very Low Birth Weight Infant, run by Children's National Research Institute 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 4 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: looking for participants now, as of the sponsor's last update on 11 Jul 2025. 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?
Contact Catherine Limperopoulos, Ph.D. (202-476-5293, CLimpero@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight Gain Velocity (time frame: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jul 2025.