Clinical trial NCT04055363: Human Milk Oligosaccharides (HMOs) Post-market Study on Infants
Official title: Growth and Feeding Tolerance of Infants Consuming a Formula Supplemented With Human Milk Oligosaccharides (HMOs): An Uncontrolled, Open-label, Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Growth
Tolerance
Adverse Event
Disorder of Intestine
Disorder Lung
Keywords: Growth
Tolerance
Adverse Event
Gastrointestinal disorder
Respiratory infection
Gastrointestinal infection
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
Collaborators: name: Puerta de Hierro University Hospital
name: University of Navarrra Hospital (Clinica Universitaria)
name: Grupo Pulso
name: Casa de la Salud Hospital
name: Vitha Santa Catalina Hospital
name: Quirón-Dexeus Universitary Hospital
name: Hospital Ruber Internacional
name: Grupo Hispalense de Pediatría Hospital
name: MH Belén Maternal Hospital
First posted: 2019-08-13
Enrollment: 207
Sex: ALL
Minimum age (years): 7
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Human milk oligosaccharides (HMOs) represent the third largest solid component of breast milk. Technology advancements made it possible to supplement infant formulas with HMOs (2'FL, LNnT). Two published RCTs have demonstrated that infant formulas supplemented with 2'FL or 2'FL+LNnT are safe, well-tolerated, support normal grow, and may support healthy GI function and confer immune benefits. The performance of HMOs-supplemented formulas assessed in a real-world setting is complementary to previously conducted RCTs conducted in highly controlled clinical settings. Main objectives will be to monitor the safety \& tolerance of HMOs-supplemented formulas in larger and diverse infant populations; to assess the performance of HMOs-supplemented formulas in mixed-fed infants, a population that was not studied in previous RCTs but likely represents a relatively common feeding regimen. Finally, considering the potential health/immune benefits of HMOs, it is also important explore the incidences of illnesses (i.e., respiratory illnesses, GI illnesses, and fever) associated with consuming HMOs-supplemented formulas and compare with breastfed infants data.

Detailed description: Objectives:

The main objective of this study is to document the growth and feeding tolerance of healthy term infants consuming an infant formula supplemented with HMOs for 8 weeks (56 days), in a real-world setting.

Main endpoints:

1. Growth documented via monitoring the anthropometric parameters including weight, length, head circumference, BMI and their corresponding z-scores (i.e., z-scores for weight-for-age, length-for-age, weight-for-length, head circumference-for-age, and BMI-for-age) calculated using the 2006 WHO Growth Standards
2. Feeding tolerance assessed via monitoring parent-reported overall GI symptom burden measured by the Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score (13-item summary score)

Additional objectives:

To describe the following outcomes in infants fed an infant formula supplemented with HMOs:

1. Formula acceptability
2. Despite there are no expected safety concerns, standard Adverse Events (AEs) monitoring will be implemented during the study

Additional endpoints:

1. Formula acceptability assessed by the Study Formula Satisfaction Questionnaire
2. Reported AEs and Serious Adverse Events (SAEs) including type, incidence, severity, seriousness and relation to study formula consumption as well as concomitant medications and non-pharmacological treatments.

   * Select morbidities of interest (i.e., respiratory illnesses, GI illnesses, and fever) will be collected as part of AE reporting and specific corresponding AE guidance forms will be used to standardize reporting of such AEs

Trial design:

Uncontrolled, single arm, open-label, prospective study in infants (enrolled at postnatal age 7 days to 2 months) fed the study formula for 8 weeks (56 days)

A group of exclusively breastfed infants (BF) will serve as a reference group in parallel to the study arm. For the BF group, Infants must have been exclusively consuming breast milk since birth, and their parent(s) must have made the decision to continue exclusively breastfeeding until at least 4 month of age

Trial population:

Healthy, male and female, term infants, 7 days postnatal age to 2 months of age at the enrollment

Treatment duration:

Total study participation/intervention up to approximately 8 weeks

Eligibility criteria: Inclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s) have been informed of all pertinent aspects of the study
2. Parent(s) are willing and able to fulfill the requirements of the study protocol
3. Healthy full term (37-42 weeks gestation) infant
4. Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months
5. Parent(s) must have independently elected, before enrollment, to formula feed

Exclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s) have been informed of all pertinent aspects of the study
2. Parent(s) are willing and able to fulfill the requirements of the study protocol
3. Healthy full term (37-42 weeks gestation) infant
4. Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months
5. Infants must have been exclusively consuming breast milk since birth, and their parent(s) must have made the decision to continue exclusively breastfeeding until at least 4 month of age

Primary outcomes:
measure: World Health Organization (WHO) based weight-for-age z-scores
timeFrame: 8 weeks (study end)
measure: World Health Organization (WHO) based length-for-age z-scores
timeFrame: 8 weeks (study end)
measure: World Health Organization (WHO) weight-for-length z-scores
timeFrame: 8 weeks (study end)
measure: World Health Organization (WHO) head-circumference-for-age z-scores
timeFrame: 8 weeks (study end)
measure: World Health Organization (WHO) based body-mass-index (BMI)-for-age z-scores
timeFrame: 8 weeks (study end)
measure: Feeding tolerance
timeFrame: 4 weeks (study midpoint)
measure: Feeding tolerance
timeFrame: 8 weeks (study end)
Secondary outcomes:
measure: Formula acceptability
timeFrame: 4 weeks (study midpoint), 8 weeks (study end)
measure: Standard adverse events (AEs) reporting for safety assessment
timeFrame: From the time the informed consent form has been signed at enrollment infant age less than 7 days to 2 months through the 8 weeks of intervention
measure: Weight
timeFrame: 8 weeks (study end)
measure: Length
timeFrame: 8 weeks (study end)
measure: Head circumference
timeFrame: 8 weeks (study end)
measure: Body-mass-index (BMI)
timeFrame: 8 weeks (study end)
Other outcomes:
Locations:
city: Las Palmas De Gran Canaria
country: Spain
facility: Vitha Santa Catalina Hospital
state: Canarias
city: Coruña
country: Spain
facility: Hospital Maternal MH Belén
state: Galicia
city: Barcelona
country: Spain
facility: Universitary Hospital Quirón-Dexeus
city: Madrid
country: Spain
facility: Ruber Internacional Clinic
city: Sevilla
country: Spain
facility: Hispalense Group
city: Valencia
country: Spain
facility: Casa de la Salud, Hospital
Study officials:
References:
citation: Storm HM, Shepard J, Czerkies LM, Kineman B, Cohen SS, Reichert H, Carvalho R. 2'-Fucosyllactose Is Well Tolerated in a 100% Whey, Partially Hydrolyzed Infant Formula With Bifidobacterium lactis: A Randomized Controlled Trial. Glob Pediatr Health. 2019 Mar 15;6:2333794X19833995. doi: 10.1177/2333794X19833995. eCollection 2019.