Human Milk Oligosaccharides (HMOs) Post-market Study on Infants

Not Applicable

Completed

• Conditions: Growth; Disorder of Intestine; Disorder Lung; Tolerance; Adverse Event
• Interventions: Other: HMO-supplemented infant formula

• Registration Number: NCT04055363
• Lead Sponsor: Société des Produits Nestlé (SPN)

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

Study Timeline

• Study Start: 2018-10-01
• Primary Completion: 2018-11-30
• Study Completion: 2018-12-31
• Study First Submitted: 2019-07-11
• Status Verified: 2019-08
• Study First Submitted QC: 2019-08-12
• Last Update Submitted: 2019-08-12
• Study First Posted: 2019-08-13
• Last Update Posted: 2019-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 207

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mixed-fed infants	HMO-supplemented infant formula	Infants receiving breastmilk and experimental formula
Formula-fed infants	HMO-supplemented infant formula	Infants fed exclusively with experimental formula

Primary Outcome Measures

Name	Time	Method
World Health Organization (WHO) based weight-for-age z-scores	8 weeks (study end)	Weight-for-age z-scores using WHO growth standards
World Health Organization (WHO) based length-for-age z-scores	8 weeks (study end)	Length-for-age z-scores using WHO growth standards
World Health Organization (WHO) weight-for-length z-scores	8 weeks (study end)	Weight-for-length z-scores using WHO growth standards
World Health Organization (WHO) head-circumference-for-age z-scores	8 weeks (study end)	head-circumference-for-age z-scores using WHO growth standards
World Health Organization (WHO) based body-mass-index (BMI)-for-age z-scores	8 weeks (study end)	Weight and height will be combined to calculate BMI in kg/m\^2, then BMI-for-age z-scores will be derived using WHO growth standards
Feeding tolerance	8 weeks (study end)	The Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score will be used to assess GI distress. This is a validated 13-item questionnaire where each item is scored on a scale of 1 to 5 with higher values indicating greater GI distress. A composite IGSQ score is derived from summing the individual scores with a possible range of 13 to 65 where higher values indicate greater GI distress and values ≤23 indicate no digestive distress.

Secondary Outcome Measures

Name	Time	Method
Formula acceptability	4 weeks (study midpoint), 8 weeks (study end)	Study Formula Satisfaction Questionnaire
Standard adverse events (AEs) reporting for safety assessment	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	Reported adverse events (AEs) and Serious Adverse Events (SAEs) include type, incidence, severity, seriousness and relation to feeding
Weight	8 weeks (study end)	Weight measurements in grams
Length	8 weeks (study end)	Length measurements in centimeters
Head circumference	8 weeks (study end)	Head circumference measurements in centimeters
Body-mass-index (BMI)	8 weeks (study end)	Weight and height will be combined to report BMI in kg/m\^2

Trial Locations

Locations (6)

Vitha Santa Catalina Hospital; 🇪🇸 Las Palmas De Gran Canaria, Canarias, Spain

Hospital Maternal MH Belén; 🇪🇸 Coruña, Galicia, Spain

Universitary Hospital Quirón-Dexeus; 🇪🇸 Barcelona, Spain

Ruber Internacional Clinic; 🇪🇸 Madrid, Spain

Hispalense Group; 🇪🇸 Sevilla, Spain

Casa de la Salud, Hospital; 🇪🇸 Valencia, Spain