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

Study Overview
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Brief Summary
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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
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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: 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 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: Formula acceptability Despite there are no expected safety concerns, standard Adverse Events (AEs) monitoring will be implemented during the study Additional endpoints: Formula acceptability assessed by the Study Formula Satisfaction Questionnaire 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

Official Title
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Growth and Feeding Tolerance of Infants Consuming a Formula Supplemented With Human Milk Oligosaccharides (HMOs): An Uncontrolled, Open-label, Prospective Study

Conditions
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Growth, Tolerance, Adverse Event, Disorder of Intestine, Disorder Lung

Intervention / Treatment
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* Other: HMO-supplemented infant formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Parent(s) are willing and able to fulfill the requirements of the study protocol Healthy full term (37-42 weeks gestation) infant Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months Parent(s) must have independently elected, before enrollment, to formula feed Exclusion Criteria: 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 Parent(s) are willing and able to fulfill the requirements of the study protocol Healthy full term (37-42 weeks gestation) infant Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months 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

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formula-fed infants<br>Infants fed exclusively with experimental formula | Other: HMO-supplemented infant formula<br>* Starter Infant Formula supplemented with 1.5g/L of Human Milk Oligosaccharides<br>|
| Experimental: Mixed-fed infants<br>Infants receiving breastmilk and experimental formula | Other: HMO-supplemented infant formula<br>* Starter Infant Formula supplemented with 1.5g/L of Human Milk Oligosaccharides<br>|
| No Intervention: Breast-fed infants<br>Reference group of exclusively breastfed | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| World Health Organization (WHO) based weight-for-age z-scores | Weight-for-age z-scores using WHO growth standards | 8 weeks (study end) | 
| World Health Organization (WHO) based length-for-age z-scores | Length-for-age z-scores using WHO growth standards | 8 weeks (study end) | 
| World Health Organization (WHO) weight-for-length z-scores | Weight-for-length z-scores using WHO growth standards | 8 weeks (study end) | 
| World Health Organization (WHO) head-circumference-for-age z-scores | head-circumference-for-age z-scores using WHO growth standards | 8 weeks (study end) | 
| World Health Organization (WHO) based body-mass-index (BMI)-for-age z-scores | 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 | 8 weeks (study end) | 
| Feeding tolerance | 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. | 4 weeks (study midpoint) | 
| Feeding tolerance | 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. | 8 weeks (study end) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth, Tolerance, Adverse Event, Gastrointestinal disorder, Respiratory infection, Gastrointestinal infection