Feeding IntoleranceFortiColos-ⅡNCT03822104
Bovine Colostrum as a Human Milk Fortifier for Preterm Infants
A study testing Bovine Colostrum and FM85 in people with Feeding Intolerance and Necrotizing Enterocolitis, run by Per Torp Sangild at 2 sites in China.
Trial summary
Very preterm infants (<32 weeks gestation) show the immaturity of organs and have high nutrient requirements for growth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). Read more about this study
- Who is it for?
- Ages 5 days to 3 weeks
- Conditions the study is for
- Feeding Intolerance, Necrotizing Enterocolitis, Postnatal Growth
- What is being tested?
- Bovine Colostrum and FM85
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 2 sitesChina
- Study dates
- 1 May 2019to 8 Jul 2021
- 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 5 days to 3 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very preterm infants born between gestational age 26 + 0 and 30 + 6 weeks (from the first day of the mother's last menstrual period and/or based on fetal ultrasound)
- DM is given at the unit when MM is absent (or insufficient in amount)
- Infants judged by the attending physician to be in need of nutrient fortification, as added in the form of HMF to MM and/or DM
- Signed parental consent
Who cannot join
- Major congenital anomalies and birth defects
- Infants who have had gastrointestinal surgery prior to randomization
- Infants who have received IF prior to randomization
Trial locations and contacts
2 sites in 1 country.
China2 sites
Shenzheng Baoan Maternity and Child Healthcare Hospital (SBMCH)
Shenzhen, Guangdong, 518133
Shenzhen Nanshan People's Hospital
Shenzhen
About this study
Official title: Bovine Colostrum to Fortify Human Milk for Preterm Infants: A Randomized, Controlled Trial
Very preterm infants (<32 weeks gestation) show the immaturity of organs and have high nutrient requirements for growth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). A fast transition to full EN is important to improve gut maturation and reduce the high risk of late-onset sepsis (LOS), related to their immature immunity in gut and blood. Conversely, too fast increase of EN predisposes to feeding intolerance and necrotizing enterocolitis (NEC). Further, human milk feeding is not sufficient to support nutrient requirements for growth of very preterm infants. Thus, it remains a difficult task to optimize EN transition, achieve adequate nutrient intake and growth, and minimize NEC and LOS in the postnatal period of very preterm infants. Mother´s own milk (MM) is considered the best source of EN for very preterm infants and pasteurized human donor milk (DM) is the second choice if MM is absent or not sufficient. The recommended protein intake is 4-4.5 g/kg/d for very low birth infants when the target is a postnatal growth similar to intrauterine growth rates. This amount of protein cannot be met by feeding only MM or DM. Thus, it is common practice to enrich human milk with human milk fortifiers (HMFs, based on ingredients used in infant formulas) to increase growth, bone mineralization and neurodevelopment, starting from 7-14 d after birth and 80-160 ml/kg feeding volume per day. Bovine colostrum (BC) is the first milk from cows after parturition and is rich in protein (80-150 g/L) and bioactive components. These components may improve gut maturation, NEC protection, and nutrient assimilation, even across species. Studies in preterm pigs show that feeding BC alone, or DM fortified with BC, improves growth, gut maturation, and NEC resistance during the first 1-2 weeks, relative to DM, or DM fortified with conventional HMFs. On this background, the investigators hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers.
Read the detailed description
Objectives
- To test if fortification of human milk with BC reduces feeding intolerance compared with currently used HMF.
- To verify the safety and tolerability of BC fortification and to monitor the rates of growth, NEC and sepsis, as investigated in a parallel trial in Denmark
Trial design This study is a dual-center, non-blinded, two-armed, randomized, controlled trial.
Participants Parents to eligible very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Children's Hospital in Shenzhen, China will be asked for participation.
Sample size 68 infants per group, 136 in total
Data type Clinical data
A parallel trial on BC used as human milk fortifier is conducting in Denmark (NCT03537365)
- Conditions
- Feeding Intolerance, Necrotizing Enterocolitis, Postnatal Growth, Late-Onset Neonatal Sepsis
- Being tested
- Bovine Colostrum, FM85
- Keywords
- Very Preterm Infants, Human Milk Fortifier, Bovine Colostrum, Enteral Feeding, Nutrition, Human milk
- Medical subject headings
- Enterocolitis, Necrotizing, Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bovine ColostrumDietary supplement
Infants randomized to the intervention group will receive a maximum of 2.8 g bovine colostrum (BC, Biofiber, Gesten, Denmark), as the HMF added to 100 ml of MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants start with 1 g (0.5 g protein) BC per 100 ml human milk on the first day, increased to 2 g (1.0 g protein) on day 3, and finally 2.8 g (1.4 g protein) on day 5 if the infants only receive DM. The intervention lasts until the infants reach postmenstrual age (PMA) 35+6 weeks or in no-need of fortification due to sufficient growth, whichever comes first.
FM85Dietary supplement
Infants randomized to the control group will receive a maximum of 4 g PreNAN FM85 (Nestlé, Vevey, Switzerland) as HMF, added to 100 ml MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants starts with 1 g (0.35 g protein) FM85 per 100 ml human milk on the first day, which will be increased to 3 g (1.05 g protein) on day 3 and finally 4 g (1.4 g protein) on day 5, if the infants only receive DM. The infants will receive FM85 as the HMF as long as additional protein in the milk is needed until discharge.
| Study group | Role | What they receive |
|---|---|---|
| Bovine Colostrum / intervention group | Experimental | Preterm infants are supplemented with bovine colostrum (BC) as a fortifier to human milk. BC is the first milk from cows after parturition and is a rich source of protein (80-150 g/L) and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and growth factors. The product is supplied in a sterile, powdered form and consists of unmodified, intact BC. Receives: Dietary Supplement: Bovine Colostrum |
| FM85 / control group | Active comparator | Preterm infants are supplemented with PreNAN FM85 as fortifier to human milk. PreNAN FM85 contains partially hydrolyzed protein and maltodextrin including vitamins and minerals. The product is supplied in a powdered form. Receives: Dietary Supplement: FM85 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of feeding intolerance
Number of infants in each group diagnosed with feeding intolerance for at least once. Feeding intolerance is defined as any pause of fortification or withhold of enteral feeding.
Measured: From start of intervention until the infants reach PMA 35+6 weeks or are not in need of fortification due to sufficient growth, whichever comes first
Secondary outcomes (8)
Body weight
Weight gain in grams per kg body weight from birth to discharge. Weight at different time points will be calculated into z-scores according to a reference. Delta z-scores will be used to evaluate growth and for comparison between groups.
Measured: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Body length
Recorded as a measure of growth in cm by standardized measuring procedures
Measured: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Head circumference
Recorded as a measure of head growth in cm by standardized measuring procedures
Measured: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Incidence of necrotizing entercolitis (NEC)
Number of infants in each group diagnosed with necrotizing enterocolitis (NEC) defined as Bell's stage II or above (Kliegman \& Walsh 1987)
Measured: From the start of intervention to hospital discharge, or up to 14 weeks
Incidence of late-onset sepsis (LOS)
Number of infants in each group diagnosed with late-onset sepsis defined as clinical signs of infection >2 days after birth with antibiotic treatment for ≥5 days (or shorter than 5 days if the participant died) with or without one positive bacterial culture in blood or cerebral spinal fluid (CSF)
Measured: From the start of intervention to hospital discharge, or up to 14 weeks
Time to reach full enteral feeding
Number of days to full enteral feeding is reached - defined as the time when >150 ml/kg/d is reached and parenteral nutrition has been discontinued
Measured: From birth to hospital discharge, or up to 14 weeks
Days on parenteral nutrition
Number of days that the infant receives intravenous intakes of protein and/or lipid and/or glucose
Measured: From birth to hospital discharge, or up to 14 weeks
Length of hospital stay
Number of days in hospital, defined as days from birth until final discharge
Measured: From birth to hospital discharge, or up to 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2019
- Study start1 May 2019
- Primary completion13 Jun 2021
- Study completion8 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Feeding IntoleranceStudies 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Per Torp Sangild
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Per Torp Sangild, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Per T Sangild, Study chair, Copenhagen University Hospital, RigshospitaletPing Zhou, Principal investigator, Shenzheng Baoan Maternity and Child Healthcare Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03822104
- Sponsor's protocol ID
- FortiColos-CN
- Acronym
- FortiColos-Ⅱ
- Status last verified
- Jan 2022
- First submitted
- 17 Jan 2019
- Last updated
- 28 Jan 2022
- 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 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bovine Colostrum to Fortify Human Milk for Preterm Infants: A Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT03822104
- Acronym / sponsor ID
- FortiColos-Ⅱ / FortiColos-CN
- Conditions
- Feeding Intolerance, Necrotizing Enterocolitis, Postnatal Growth, Late-Onset Neonatal Sepsis
- Keywords
- Very Preterm Infants, Human Milk Fortifier, Bovine Colostrum, Enteral Feeding, Nutrition, Human milk
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Per Torp SangildUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 13 Jun 2021 (actual)
- Study completion
- 8 Jul 2021 (actual)
- First posted
- 30 Jan 2019 (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.
Very preterm infants (<32 weeks gestation) show the immaturity of organs and have high nutrient requirements for growth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). A fast transition to full EN is important to improve gut maturation and reduce the high risk of late-onset sepsis (LOS), related to their immature immunity in gut and blood. Conversely, too fast increase of EN predisposes to feeding intolerance and necrotizing enterocolitis (NEC). Further, human milk feeding is not sufficient to support nutrient requirements for growth of very preterm infants. Thus, it remains a difficult task to optimize EN transition, achieve adequate nutrient intake and growth, and minimize NEC and LOS in the postnatal period of very preterm infants. Mother´s own milk (MM) is considered the best source of EN for very preterm infants and pasteurized human donor milk (DM) is the second choice if MM is absent or not sufficient. The recommended protein intake is 4-4.5 g/kg/d for very low birth infants when the target is a postnatal growth similar to intrauterine growth rates. This amount of protein cannot be met by feeding only MM or DM. Thus, it is common practice to enrich human milk with human milk fortifiers (HMFs, based on ingredients used in infant formulas) to increase growth, bone mineralization and neurodevelopment, starting from 7-14 d after birth and 80-160 ml/kg feeding volume per day. Bovine colostrum (BC) is the first milk from cows after parturition and is rich in protein (80-150 g/L) and bioactive components. These components may improve gut maturation, NEC protection, and nutrient assimilation, even across species. Studies in preterm pigs show that feeding BC alone, or DM fortified with BC, improves growth, gut maturation, and NEC resistance during the first 1-2 weeks, relative to DM, or DM fortified with conventional HMFs. On this background, the investigators hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers.
Detailed description
Objectives
- To test if fortification of human milk with BC reduces feeding intolerance compared with currently used HMF.
- To verify the safety and tolerability of BC fortification and to monitor the rates of growth, NEC and sepsis, as investigated in a parallel trial in Denmark
Trial design This study is a dual-center, non-blinded, two-armed, randomized, controlled trial.
Participants Parents to eligible very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Children's Hospital in Shenzhen, China will be asked for participation.
Sample size 68 infants per group, 136 in total
Data type Clinical data
A parallel trial on BC used as human milk fortifier is conducting in Denmark (NCT03537365)
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bovine Colostrum / intervention group | Experimental | Dietary Supplement: Bovine ColostrumPreterm infants are supplemented with bovine colostrum (BC) as a fortifier to human milk. BC is the first milk from cows after parturition and is a rich source of protein (80-150 g/L) and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and growth factors. The product is supplied in a sterile, powdered form and consists of unmodified, intact BC. |
| FM85 / control group | Active comparator | Dietary Supplement: FM85Preterm infants are supplemented with PreNAN FM85 as fortifier to human milk. PreNAN FM85 contains partially hydrolyzed protein and maltodextrin including vitamins and minerals. The product is supplied in a powdered form. |
Who may qualify
- Ages
- 5 days to 3 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Very preterm infants born between gestational age 26 + 0 and 30 + 6 weeks (from the first day of the mother's last menstrual period and/or based on fetal ultrasound)
- DM is given at the unit when MM is absent (or insufficient in amount)
- Infants judged by the attending physician to be in need of nutrient fortification, as added in the form of HMF to MM and/or DM
- Signed parental consent
Key exclusion criteria (3 listed)
- Major congenital anomalies and birth defects
- Infants who have had gastrointestinal surgery prior to randomization
- Infants who have received IF prior to randomization
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 |
|---|---|---|
| Bovine ColostrumInfants randomized to the intervention group will receive a maximum of 2.8 g bovine colostrum (BC, Biofiber, Gesten, Denmark), as the HMF added to 100 ml of MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants start with 1 g (0.5 g protein) BC per 100 ml human milk on the first day, increased to 2 g (1.0 g protein) on day 3, and finally 2.8 g (1.4 g protein) on day 5 if the infants only receive DM. The intervention lasts until the infants reach postmenstrual age (PMA) 35+6 weeks or in no-need of fortification due to sufficient growth, whichever comes first. | Dietary supplement | Bovine Colostrum / intervention group |
| FM85Infants randomized to the control group will receive a maximum of 4 g PreNAN FM85 (Nestlé, Vevey, Switzerland) as HMF, added to 100 ml MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants starts with 1 g (0.35 g protein) FM85 per 100 ml human milk on the first day, which will be increased to 3 g (1.05 g protein) on day 3 and finally 4 g (1.4 g protein) on day 5, if the infants only receive DM. The infants will receive FM85 as the HMF as long as additional protein in the milk is needed until discharge. | Dietary supplement | FM85 / control group |
Primary outcome
Incidence of feeding intolerance
Time frame: From start of intervention until the infants reach PMA 35+6 weeks or are not in need of fortification due to sufficient growth, whichever comes first
Number of infants in each group diagnosed with feeding intolerance for at least once. Feeding intolerance is defined as any pause of fortification or withhold of enteral feeding.
8 secondary outcomes
Body weight
Time frame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Body length
Time frame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Head circumference
Time frame: Measured weekly from the start of intervention until hospital discharge, or up to 14 weeks
Incidence of necrotizing entercolitis (NEC)
Time frame: From the start of intervention to hospital discharge, or up to 14 weeks
Incidence of late-onset sepsis (LOS)
Time frame: From the start of intervention to hospital discharge, or up to 14 weeks
Time to reach full enteral feeding
Time frame: From birth to hospital discharge, or up to 14 weeks
Days on parenteral nutrition
Time frame: From birth to hospital discharge, or up to 14 weeks
Length of hospital stay
Time frame: From birth to hospital discharge, or up to 14 weeks
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 28 Jan 2022.
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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.
Per T Sangild study chair
Copenhagen University Hospital, Rigshospitalet
Ping Zhou principal investigator
Shenzheng Baoan Maternity and Child Healthcare Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bovine Colostrum and FM85 in people with Feeding Intolerance and Necrotizing Enterocolitis, run by Per Torp Sangild at 2 sites in China.
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: finished, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
Incidence of feeding intolerance (time frame: From start of intervention until the infants reach PMA 35+6 weeks or are not in need of fortification due to sufficient growth, whichever comes first). 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 28 Jan 2022.