Human MilkNCT03001479
Noninferiority Trial of Liquid Human Milk Fortifier (HMF) Hydrolyzed Protein Versus Liquid HMF With Supplemental Liquid Protein
A study testing Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid in people with Human Milk and Premature Birth of Newborn, run by St. Louis University at 1 site in United States.
Trial summary
Breast milk is readily accepted as the ideal source of nutrition for almost all infants, including premature or very low birth weight infants. However, these high-risk infants require the addition of fortifiers to their milk in order to achieve sufficient levels of calories, vitamins, and minerals for adequate growth. Read more about this study
- Who is it for?
- Ages Up to 2 weeks
- Conditions the study is for
- Human Milk, Premature Birth of Newborn
- What is being tested?
- Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2017to 1 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 2 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very low birth weight, premature infants admitted to the NICU at Cardinal Glennon
- <32 weeks gestational age and birthweight <1500 grams
- receiving maternal or donor breast milk
Who cannot join
- Infants with an estimated gestational age >32 weeks OR birthweight >1500 grams
- Infants who die before fortification of feedings
- Infants receiving formula
- Infants that did not receive feedings with HMF
- Infants transferred to another hospital prior to discharge
Trial locations and contacts
1 site in 1 country.
United States1 site
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
About this study
Official title: Extensively Hydrolyzed Liquid Human Milk Fortifier Versus Liquid Human Milk Fortifier With Supplemental Liquid Protein
Breast milk is readily accepted as the ideal source of nutrition for almost all infants, including premature or very low birth weight infants. However, these high-risk infants require the addition of fortifiers to their milk in order to achieve sufficient levels of calories, vitamins, and minerals for adequate growth. We are currently using a liquid human milk fortifier which does not provide sufficient protein intake, requiring addition of a liquid protein supplement. A new product has been released which provides sufficient protein in the liquid HMF, without the acidification seen in previous products.
This is a prospective, randomized noninferiority study comparing the safety and efficacy of the new HMF with additional protein to our current standard of adding additional protein supplementation on top of the HMF.
Read the detailed description
All infants admitted to the Neonatal Intensive Care Unit (NICU) at Cardinal Glennon at gestational age <32 weeks and birthweight <1500g, and whose mothers intend to use breast milk (maternal or donor) will be approached for study participation. Infants can be enrolled at any point up until their feedings become fortified, typically around the 8th day of life.
Eligible infants whose parents consent for participation will be randomized to one of the two study regimens. Sealed envelopes containing the subject treatment group will be prepared from randomization schedules that are computer-generated using a pseudorandom permuted blocks algorithm. Multiples will be randomized together to the same treatment group. The randomization will be block stratified by birth weight (500-1000g and 1001-1500g). Infants will have laboratory values to follow for signs of metabolic acidosis and nutritional status. These labs (BMP, Magnesium, Phosphorous, Alkaline Phosphatase, and prealbumin) will be drawn on study days 1, 15, and 30. Total blood volume for these labs is approximately 1.4 mL, and may be obtained by venipuncture or heel stick. These labs are monitored for nutritional sufficiency in very low birth weight infants already, the only change will be the timing that the labs are obtained.
Infants will remain on their designated HMF until one of 3 different time points: 1) Infant does not tolerate HMF and must be taken off, 2) Infant is no longer receiving breastmilk and is transitioned to a premature formula, or 3) Infant is getting ready to go home and HMF is removed from the feedings.
Hospitalization data will be collected on the infants until they are either discharged from the NICU or until they reach 36 weeks corrected gestational age, whichever occurs first. Data collected will include: birthweight, gestational age, gender, antenatal steroids, APGARs, days of parenteral nutrition, day enteral feedings were initiated, daily enteral volume intake, daily caloric and protein intake, day of HMF and/or liquid protein initiation. Lab data will be recorded as noted above. Growth data will be recorded by daily weights and weekly head circumferences and lengths. Intolerance will be assessed by incidence of feeding intolerance, nil per os (NPO) time, change in diet due to intolerance, incidence of metabolic acidosis, incidence of necrotizing enterocolitis, incidence of spontaneous intestinal perforation, cause of death, and length of hospital stay. Data on NICU complications, including late onset sepsis, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, and use of postnatal steroids (which can affect growth) will also be recorded.
Neurodevelopmental data will be collected on the infants from their first Bayley evaluation in the Nursery Follow-up clinic, usually performed at 15-18 months of age. We will record cognitive, language, and motor scores. We will also collect information on therapy services received, and incidence of blindness or deafness.
- Conditions
- Human Milk, Premature Birth of Newborn
- Being tested
- Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Similac Human Milk Fortifier Hydrolyzed Protein Concentrated LiquidDietary supplement
HMF with additional hydrolyzed protein
| Study group | Role | What they receive |
|---|---|---|
| Standard: Liquid HMF and liquid protein | No intervention | This is our standard breast milk fortification in our NICU. One packet (5 mL) of Similac Human Milk Fortifier Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. After infants reach full feedings (160 ml/kg/d), 3 ml/kg of Similac Liquid Protein Fortifier is added (0.5 g/kg protein). This is increased to 6 ml/kg (1 g/kg protein) the next day. |
| Intervention: HMF Hydrolyzed Protein Concentrated Liquid | Experimental | One packet (5 mL) of Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. Feedings then continue to be advanced to full volume (160 ml/kg/d). Receives: Dietary Supplement: Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight gain, short term
(grams) in first 30 days on HMF
Measured: 30 days
Length, short term
(cm) in first 30 days on HMF
Measured: 30 days
Head circumference, short term
(cm) in first 30 days on HMF
Measured: 30 days
Secondary outcomes (5)
Weight gain, long term
Weight (grams) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first
Measured: 36 weeks gestational age or time of hospital discharge
Length, long term
Length (cm) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first
Measured: 36 weeks gestational age or time of hospital discharge
Head circumference, long term
Head circumference (cm) at 36 weeks corrected gestational age or time of hospital discharge, whichever is first
Measured: 36 weeks gestational age or time of hospital discharge
feeding intolerance
Signs of feeding intolerance, including loose stools, emesis, metabolic acidosis, necrotizing enterocolitis. Presence or absence of symptoms.
Measured: 30 days
neurodevelopmental outcomes
Bayley Scales of Infant Development III at 18 months of corrected gestational age
Measured: 18 months corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2016 (estimated)
- Study start13 Mar 2017
- Primary completion1 May 2020
- Study completion1 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human MilkStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Louis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Catherine Cibulskis, MD, St. Louis University
- Investigators
- Catherine C Cibulskis, MD, Principal investigator, St. Louis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03001479
- Sponsor's protocol ID
- 27563
- Status last verified
- May 2023
- First submitted
- 20 Sep 2016
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extensively Hydrolyzed Liquid Human Milk Fortifier Versus Liquid Human Milk Fortifier With Supplemental Liquid Protein
- ClinicalTrials.gov ID
- NCT03001479
- Acronym / sponsor ID
- 27563
- Conditions
- Human Milk, Premature Birth of Newborn
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- St. Louis UniversityUniversity, hospital or other
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 1 May 2020 (actual)
- Study completion
- 1 May 2023 (actual)
- First posted
- 23 Dec 2016 (estimated)
- 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.
Breast milk is readily accepted as the ideal source of nutrition for almost all infants, including premature or very low birth weight infants. However, these high-risk infants require the addition of fortifiers to their milk in order to achieve sufficient levels of calories, vitamins, and minerals for adequate growth. We are currently using a liquid human milk fortifier which does not provide sufficient protein intake, requiring addition of a liquid protein supplement. A new product has been released which provides sufficient protein in the liquid HMF, without the acidification seen in previous products.
This is a prospective, randomized noninferiority study comparing the safety and efficacy of the new HMF with additional protein to our current standard of adding additional protein supplementation on top of the HMF.
Detailed description
All infants admitted to the Neonatal Intensive Care Unit (NICU) at Cardinal Glennon at gestational age <32 weeks and birthweight <1500g, and whose mothers intend to use breast milk (maternal or donor) will be approached for study participation. Infants can be enrolled at any point up until their feedings become fortified, typically around the 8th day of life.
Eligible infants whose parents consent for participation will be randomized to one of the two study regimens. Sealed envelopes containing the subject treatment group will be prepared from randomization schedules that are computer-generated using a pseudorandom permuted blocks algorithm. Multiples will be randomized together to the same treatment group. The randomization will be block stratified by birth weight (500-1000g and 1001-1500g). Infants will have laboratory values to follow for signs of metabolic acidosis and nutritional status. These labs (BMP, Magnesium, Phosphorous, Alkaline Phosphatase, and prealbumin) will be drawn on study days 1, 15, and 30. Total blood volume for these labs is approximately 1.4 mL, and may be obtained by venipuncture or heel stick. These labs are monitored for nutritional sufficiency in very low birth weight infants already, the only change will be the timing that the labs are obtained.
Infants will remain on their designated HMF until one of 3 different time points: 1) Infant does not tolerate HMF and must be taken off, 2) Infant is no longer receiving breastmilk and is transitioned to a premature formula, or 3) Infant is getting ready to go home and HMF is removed from the feedings.
Hospitalization data will be collected on the infants until they are either discharged from the NICU or until they reach 36 weeks corrected gestational age, whichever occurs first. Data collected will include: birthweight, gestational age, gender, antenatal steroids, APGARs, days of parenteral nutrition, day enteral feedings were initiated, daily enteral volume intake, daily caloric and protein intake, day of HMF and/or liquid protein initiation. Lab data will be recorded as noted above. Growth data will be recorded by daily weights and weekly head circumferences and lengths. Intolerance will be assessed by incidence of feeding intolerance, nil per os (NPO) time, change in diet due to intolerance, incidence of metabolic acidosis, incidence of necrotizing enterocolitis, incidence of spontaneous intestinal perforation, cause of death, and length of hospital stay. Data on NICU complications, including late onset sepsis, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, and use of postnatal steroids (which can affect growth) will also be recorded.
Neurodevelopmental data will be collected on the infants from their first Bayley evaluation in the Nursery Follow-up clinic, usually performed at 15-18 months of age. We will record cognitive, language, and motor scores. We will also collect information on therapy services received, and incidence of blindness or deafness.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard: Liquid HMF and liquid protein | No intervention | –This is our standard breast milk fortification in our NICU. One packet (5 mL) of Similac Human Milk Fortifier Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. After infants reach full feedings (160 ml/kg/d), 3 ml/kg of Similac Liquid Protein Fortifier is added (0.5 g/kg protein). This is increased to 6 ml/kg (1 g/kg protein) the next day. |
| Intervention: HMF Hydrolyzed Protein Concentrated Liquid | Experimental | Dietary Supplement: Similac Human Milk Fortifier Hydrolyzed Protein Concentrated LiquidOne packet (5 mL) of Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid is added to breast milk feedings when infants reach 100 ml/kg/day. A second packet is added the next day (10 mL total), to make 24 kcal/oz. Feedings then continue to be advanced to full volume (160 ml/kg/d). |
Who may qualify
- Ages
- Up to 2 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Very low birth weight, premature infants admitted to the NICU at Cardinal Glennon
- <32 weeks gestational age and birthweight <1500 grams
- receiving maternal or donor breast milk
Key exclusion criteria (5 listed)
- Infants with an estimated gestational age >32 weeks OR birthweight >1500 grams
- Infants who die before fortification of feedings
- Infants receiving formula
- Infants that did not receive feedings with HMF
- Infants transferred to another hospital prior to discharge
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 |
|---|---|---|
| Similac Human Milk Fortifier Hydrolyzed Protein Concentrated LiquidHMF with additional hydrolyzed protein | Dietary supplement | Intervention: HMF Hydrolyzed Protein Concentrated Liquid |
Primary outcome
Weight gain, short term
Time frame: 30 days
(grams) in first 30 days on HMF
Length, short term
Time frame: 30 days
(cm) in first 30 days on HMF
Head circumference, short term
Time frame: 30 days
(cm) in first 30 days on HMF
5 secondary outcomes
Weight gain, long term
Time frame: 36 weeks gestational age or time of hospital discharge
Length, long term
Time frame: 36 weeks gestational age or time of hospital discharge
Head circumference, long term
Time frame: 36 weeks gestational age or time of hospital discharge
feeding intolerance
Time frame: 30 days
neurodevelopmental outcomes
Time frame: 18 months corrected gestational age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
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Healthy Volunteers
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.
Catherine C Cibulskis, MD principal investigator
St. Louis University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid in people with Human Milk and Premature Birth of Newborn, run by St. Louis University 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 5 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: finished, as of the sponsor's last update on 6 May 2023. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Weight gain, short term (time frame: 30 days). The study lists 3 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 6 May 2023.