Clinical trial NCT04413994: Exclusive Human-milk in Preterm NEOnates and Early VASCular Aging Risk Factors (NEOVASC)
Official title: Effects of an Exclusive Human-milk Diet in Preterm NEOnates on Early VASCular Aging Risk Factors (NEOVASC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prematurity
Vascular Aging
Lead sponsor: Prolacta Bioscience
Sponsor class: INDUSTRY
Collaborators: name: Medical University of Vienna
name: Federal University Teaching Hospital, Feldkirch, Austria
name: Paracelsus Medical University
First posted: 2020-06-04
Enrollment: 200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The NEO-VASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial.
Primary purpose: TREATMENT

Brief summary: Early vascular aging has its origins in fetal and neonatal life. The NEOVASC clinical trial aims to determine the effects of an exclusive human milk diet in extremely preterm infants on long-term cardiovascular health.

Detailed description: Early vascular aging has its origins in fetal and neonatal life. This early period of life plays an important role in the development of obesity, high blood pressure, abnormalities in lipid metabolism and non-insulin dependent diabetes. Increased cardiovascular risk in formerly preterm infants constitutes a health problem of steadily growing relevance. Emerging evidence suggests that human milk feeding has substantial benefits to the health of all infants, especially for those born prematurely. Unfortunately, human milk alone does not provide sufficient concentrations of nutrients, especially calcium, phosphorus, protein, and fat needed for these infants to grow satisfactorily. For that purpose, fortifiers are used to help increase the nutritional value of human milk.

The NEOVASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial. A total of 200 extremely preterm infants and 100 term infants are recruited for the test and control group, respectively. Infants in the test group (i.e., premature neonates) are randomized to either:

1. An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and a human milk fortifier until 36 weeks of gestation; OR
2. Human milk (as long as available) and a human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula.

After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included. Participants within this control group are not enrolled at the time of birth but instead recruited in various kindergartens at the age of five. Therefore, data from birth is taken from the mother-child-booklet, which contains clinical records about the pregnancy, birth and early life of children born in Austria. The total study duration is scheduled for 96 months with a recruitment phase of 36 months. Follow-up visits are planned at one, two and five years of age for the test group.

The purpose of the NEOVASC clinical trial is to characterize early life stressors by assessing the effects of a physiological (i.e., human milk-based) nutrition in extremely preterm infants during the vulnerable preterm period on the risk of metabolic and vascular complications in later life. Outcomes include predictors and intermediate components of cardiovascular disease.

Eligibility criteria: Preterm-born group:

Inclusion Criteria:

1. Extremely preterm infants with a birth weight of 500-1250g.
2. Feeding is NPO or exclusive human milk prior to enrollment.
3. Parent(s) willing to sign informed consent.-

Exclusion Criteria:

1. Infants with a birth weight \<500g or \>1250g
2. Subjects diagnosed with inborn errors of metabolism such as galactosemia, phenylketonuria
3. Subjects who have not been NPO or fed exclusive human milk diet prior to enrollment.
4. Presence of major congenital malformation.
5. Presence of intestinal perforation or Stage 2 Necrotizing enterocolitis prior to enrollment.
6. Parent(s) not willing to sign informed consent.
7. Unable to participate for any reason based on the decision of the study investigator (e.g. unlikely to survive the study period).

Term-born group:

Inclusion criteria

1. Term-born children with an adequate birth weight
2. Parent(s) willing to sign informed consent

Exclusion criteria

1. Subjects with acute or chronic illness
2. Parent(s) not willing to sign informed consent

Primary outcomes:
measure: Fasting blood glucose
timeFrame: "First day of life" up to "five years"
measure: Blood pressure
timeFrame: "First day of life" up to "five years"
measure: Distensibility of aorta
timeFrame: "First day of life" up to "five years"
Secondary outcomes:
measure: Fasting blood glucose
timeFrame: "First day of life" up to "24 months"
measure: Blood pressure
timeFrame: "First day of life" up to "24 months"
measure: BMI
timeFrame: "First day of life" up to "five years"
measure: Insulin sensitivity
timeFrame: "First day of life" up to "five years"
measure: Lipid profile
timeFrame: "First day of life" up to "five years"
Other outcomes:
measure: Fasting blood glucose
timeFrame: "five years of age"
measure: Blood pressure
timeFrame: "five years of age"
measure: Distensibility of the descending aorta
timeFrame: "five years of age"
measure: BMI
timeFrame: "five years of age"
measure: Insulin sensitivity
timeFrame: "five years of age"
measure: Lipid profile
timeFrame: "five years of age"
Locations:
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
state: Tyrol
Study officials:
affiliation: Medical University of Innsbruck
name: Ursula Kiechl-Kohlendorfer, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mitterer W, Binder C, Blassnig-Ezeh A, Auer-Hackenberg L, Berger A, Simma B, Wald M, Lee M, Kiechl-Kohlendorfer U. Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial. Trials. 2021 Jul 31;22(1):509. doi: 10.1186/s13063-021-05445-9.