To investigate the effects of a partially hydrolysed protein based infant formula (pHPformula) in healthy term infants until 17 weeks of age on growth, blood parameters, safety,and gastro intestinal tolerance compared to standard infant formula.…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Growth, Weight gain
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome parameter in this study is weight gain in grams per day
from baseline until 17 weeks of age.
Secondary outcome
Gain from baseline until 17 weeks of age of
* Recumbent length (mm/day)
* Head circumference (mm/day)
* Mid-upper arm circumference (mm/day)
Z-scores of anthropometric parameters at 17 weeks of age:
* Weight-for-age
* Weight-for-length
* Length-for-age
* Body Mass Index (BMI)-for-age
* Head circumference-for-age
* Mid-upper arm circumference-for-age as of 13 weeks of age
Blood parameters assessed at 17 weeks of age:
* Albumin
* Serum mineral markers: calcium, phosphorus, iron and magnesium
* Blood Urea Nitrogen
These parameters will only be measured in blood of infants, whose parents gave
additional
consent to draw blood.
Safety parameters from baseline until 17 weeks of age as measured by:
* Number, type and severity of (Serious) Adverse events and possible
relatedness to study
product
* Use of (co-)medication
Gastrointestinal tolerance parameters from baseline until 17 weeks of age
including:
* Occurrence and severity of gastrointestinal symptoms:
- regurgitation (return of the milk into the mouth without force)
- vomiting (return of the milk into the mouth with force)
* Stool frequency
* Stool consistency
* Occurrence of diarrhoea
* Occurrence of constipation
Background summary
It is universally accepted that the optimal nutrition for a newborn infant is
breast milk. Consequently,
exclusive breastfeeding is the preferred mode of feeding for all term new born
infants and the World
Health Organisation therefore recommends exclusive breastfeeding for at least 6
months. Breast milk
provides a complete supply of nutrients to support growth and development in
early life. Breast milk
contains bioactive components that beneficially affect intestinal health, gut
microbial colonization and
immune maturation.
When a mother is unable to breastfeed her infant, or chooses not to breastfeed,
an infant formula
following the composition of mature breast milk is recognized as the best
alternative. Research to
improve the quality of infant milk formulas is aimed at mimicking the
composition of breast milk, but
above all at achieving the functional effects that are observed in breastfed
infants. One of the
important functional effects of breast milk is prevention of allergies.
Breastfeeding is considered to be
one of the main pillars in allergy prevention. Consequently in the last
decades, to get as close as
possible to this functional benefit of breast milk, development of infant
nutrition to prevent allergies has
been a major field of interest with an important role for hydrolysed proteins.
In a (partially) hydrolysed protein formula, the cow*s milk protein is
enzymatically hydrolysed (fragmented) with the goal to
reduce protein size and as such allergenicity of the proteins.
Current international evidence-based guidelines, recommend formula with such
partially hydrolysed
proteins for infants at risk of allergy, defined by family history, for the
first 4-6 months if breastfeeding is
insufficient or not possible. It is considered a good option for these infants,
because the small milk
protein fragments are more likely to be recognized as harmless by the immune
system.
However, recently this preventive effect on developing allergies has been
challenged in a meta-analysis. This indicates that the effect of partially
hydrolysed formula on the development of allergic disease
needs better understanding on intervention period, target population and
outcome parameter to
determine whether the modest effects of hydrolysed formula on the incidence of
allergic manifestations
can be confirmed.
Apart from the fact that it is necessary to gain more insight in the effect of
hydrolysed proteins on
allergy risk reduction, it is also necessary to ensure healthy growth and
nutritional value. In particular
because large variations exist in the composition of hydrolysed formula in the
source of macro-nutrients
and (protein) levels. In addition, hydrolysed formula may impact the food
intake compared to intact
formula possibly due to sensory taste and the large amount of free amino acid
of which some may
influence satiety. So far, studies demonstrated no evidence for long-term
effect on growth or body
composition of hydrolysed formulas in healthy infants without family allergic
history. On the
other hand, the GINI study gives indication of a slower BMI development in
healthy infants with family
allergic history who received extensively hydrolysed casein formula during
first year of life compared to
infants on extensively and partially hydrolysed whey based formula, cows* milk
formula or breast milk.
Whether hydrolysed formulas in the Nutricia portfolio have an effect on growth,
either with extensively
hydrolysed or partially hydrolysed proteins, was studied for example by
comparing different levels of
hydrolysed proteins (Giraffe: internal report) and by investigating the effect
of adding synbiotics to
extensively hydrolysed proteins. Both studies indicated that the products were
safe, well tolerated
and support an adequate growth in infants fed (extensively) hydrolysed formula
compared to the WHO
growth standards. However, a head-to-head comparison of the effect of partially
hydrolysed proteins
versus intact proteins and breastfeeding on growth and safety parameters was
not performed.
The primary aim of this study therefore is to evaluate the safety and
nutritional adequacy of a hydrolysed
protein formula compared to an intact protein formula and to breastfeeding as a
reference on growth
until 17 weeks of age.
Study objective
To investigate the effects of a partially hydrolysed protein based infant
formula (pHP
formula) in healthy term infants until 17 weeks of age on growth, blood
parameters, safety,
and gastro intestinal tolerance compared to standard infant formula.
Primary:
The primary objective of this study is to investigate equivalence of weight
gain per day from baseline until the age of 17 weeks in infants receiving
partially hydrolysed proteins (test
product) compared to infants receiving intact proteins (control product).
Secondary:
The secondary objectives of this study are:
- To investigate equivalence of weight gain per day in infants receiving
formula containing
partially hydrolysed proteins compared to infants receiving breast milk from
baseline until the
age of 17 weeks;
-To investigate equivalence of other growth parameters (recumbent length, head
circumference, mid upper arm circumference) in infants receiving formula
containing partially
hydrolysed proteins compared to infants receiving formula containing intact
proteins or infants
receiving breast milk from baseline until the age of 17 weeks;
- To investigate equivalence of other growth z-scores parameters (weight-for-
age, weight-for length, length-for-age, BMI-for-age,head circumference-for-age,
mid upper arm circumference) in infants receiving formula containing partially
hydrolysed proteins compared to infants
receiving formula containing intact proteins or infants receiving breast milk
at the age of 17 weeks;
- To investigate the effect on blood parameters in infants receiving formula
containing partially
hydrolysed proteins compared to infants receiving formula containing intact
proteins or infants
receiving breast milk at the age of 17 weeks;
- To assess the effect on safety in infants receiving partially hydrolysed
proteins compared to
infants receiving formula containing intact proteins or infants receiving
breast milk from
baseline until the age of 17 weeks;
- To assess the effect on gastrointestinal tolerance in infants receiving
formula containing
partially hydrolysed proteins compared to infants receiving formula containing
intact proteins or
infants receiving breast milk from baseline until the age of 17 weeks.
Study design
This is a randomised, controlled, double blind, parallel group, multi-country,
Phase IIb study.
The study consists of 2 infant formula arms i.e.:
- Test product: Partially hydrolysed 100 percent whey protein based infant
formula
containing scGOS/lcFOS.
-Control product: Intact cow*s milk protein based infant formula (whey:casein
ratio of
60:40) containing scGOS/lcFOS.
In addition, a breastfeeding arm is added to be used as a reference arm.
Intervention
After parent(s)/legal guardian(s) have agreed to and signed informed consent,
infants may enrol in the study. Infants, whose mother has the intention to
breastfeed her infant until the infants* age of 17 weeks, may be enrolled in
the breastfeeding reference arm. Infants, whose mother has the intention to
exclusively formula feed her infant as of 14 days of age at the latest, may be
randomised to one of the infant formula arms. Infants will enrol in the study
as soon as they pass the eligibility check.
At a maximum age of 14 days all infants will have a screening/randomisation
visit (Visit 1), followed by four follow up visits when the infant is 4 (Visit
2), 8 (Visit 3), 13 (Visit 4) and 17 weeks of age (Visit 5). At the infants*
age of 19 weeks the Investigator performs a phone call (PC) to parents of all
participating infants to follow up e.g. on safety and outstanding issues,
adverse events or transition to commercial product.
During the seven days before Visit 2, 3, 4 and 5, parent(s)/caretaker(s) of all
infants are requested to fill out an eDiary on daily basis. The eDiary collects
data on the intake of study products or breastfeeding, the infants* defecation
pattern and aspects of gastro intestinal tolerance. Parent(s)/legal guardian(s)
or caretaker(s) will receive automatic reminders from the eDiary system to fill
out the diary.
Infants eligible for the infant formula arms
As soon as an infant is exclusively formula fed the screening/randomisation
visit (Visit 1) takes place. At that time point, the infant will have a maximum
age of 14 days. After eligibility assessment, eligible infants will be
randomised in a double-blinded manner to receive either the test product or the
control product until the age of 17 weeks. This means that the infant receives
the test or control product for a minimum duration of 15 weeks to a maximum
duration of 17 weeks, depending on the age at randomisation. At Visit 1, the
Investigator collects also baseline data
on demographics, medical and social information, and anthropometrics. In
addition, the Investigator provides the study product, gives instructions to
the parents on how to use the eDiary and plans the next study visit.
At each of the following visits, the Investigator collects data on
anthropometrics, study product intake, compliance with the study protocol,
information on (Serious) Adverse Events, and information of use of medication
and nutritional supplements. To support collection of data for the eCRF on
intake of study product, the Investigator may use the data filled out by the
parents in the eDiary the week before each study visit as a tool for the
discussion. Likewise, data on gastro intestinal tolerance in the eDiary may be
used to support the assessment of e.g. adverse events related to gastro
intestinal tolerance during the visits.
At visit 5, in addition to follow-up assessments the Investigator will draw a
venous blood sample (1.4mL) for assessment of plasma proteins and mineral
status parameters, of infants whose parent(s)/legal guardian(s) provide
informed consent for a blood sample on a voluntary base.
Infants eligible for the breastfeeding reference arm
As soon as parents or legal guardian(s) give informed consent, infants will
have an eligibility assessment and enrol, if meeting the in- and exclusion
criteria, in the study. The maximum age at enrolment is 14 days of age. These
infants follow the same visit schedule and study assessments as
the randomised infants as described above, including completion of the eDiaries
and blood sampling (if separate informed consent for taking a blood sample is
given). In case parents/ caretakers cannot use eDiaries, data will be collected
via paper diaries.
Study burden and risks
Time spent
4/5 extra hospital visits.
Risk of infant formula
Infants who participate in one of the Infant Formula groups receive an infant
formula that is already on the market for more than 10 years. Therefore no
major risks or disadvantages are expected for participants compared to infants
who do not participate in this study. A general risk is that these formulas
contain proteins derived from cow*s milk. These proteins can cause allergic
reactions in infants who have a cow*s milk, soy oil or fish oil allergy. For
infants who appear to have a cow*s milk, soy or fish allergy, participation
will be reassessed by the doctor. Both types of formula contain lactose and are
therefore not suitable for infants with lactose intolerance.
Infants might have softer stools due to the non-digestible fibres in these
formulas compared to breastfed infants or other commercially available infant
formula.
Risk of blood sample
After consent, a blood sample of infant can be collected, this will be done by
appropriately trained and experienced staff. Prior to the collection of the
blood sample, numbing cream may be applied to reduce discomfort. The procedure
may be slightly painful to the infant and may cause bruising at the site of the
needle puncture. In rare cases, an infection may occur at the puncture site
after blood collection.
Uppsalalaan 12
Utrecht 3584 CT
NL
Uppsalalaan 12
Utrecht 3584 CT
NL
Listed location countries
Age
Inclusion criteria
1. Healthy term infants (gestational age * 37 weeks + 0 days and * 41 weeks + 6 days);
2. Infants* age at enrolment * 14 days;
3. Birth weight within normal range for gestational age and sex (10th to 90th percentile according
to the WHO Child Growth Standards * or local growth standards if available);
4. Head circumference at inclusion within normal range for age and sex (within 2 SD curves
according to WHO Child Growth Standards * or local growth standards if available);
5. Infant formula arms: infants who are exclusively formula fed by time of randomisation with a
maximum infants* age of 14 days (infants of mothers who choose not to breastfeed or mothers
who cease breastfeeding for any reason before the infant is 14 days of age);
OR
Breastfeeding reference arm: infants who are exclusively breastfed and whose mothers are
intending to exclusively breastfeed their infant at least until the infant is 17 weeks of age;
6. Written informed consent from parent(s) and/or legal guardian(s) aged * 18 years.
Exclusion criteria
Infants of pregnant women/mothers:
1. who are currently participating or will participate in any other (clinical) study involving
investigational or marketed products during pregnancy and/or lactation;
2. known to have a significant medical condition (including during pregnancy) that might interfere
with the study or known to affect intra-uterine growth (e.g. placenta previa, pre-eclampsia,
eclampsia, gestational diabetes requiring insulin or oral medication), as per investigator*s
clinical judgement;
Infants of parents:
3. who are incapable to comply with study protocol or Investigator's uncertainty about the
willingness or ability of the parents to comply with the protocol requirements;
Infants:
4. who have to be fed with a special diet other than standard (non-hydrolysed) cow*s milk based
infant formula
5. known to have current or previous illnesses/conditions which could interfere with the study or
its outcome parameters, such as gastrointestinal malformations, congenital metabolic
disorders, immune deficiency or major surgery, as per investigator*s clinical judgement;
6. with any history of, or current participation in any other study involving investigational or
marketed products.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03062761 |
| CCMO | NL61257.056.17 |