Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Second Generation Human Milk Oligosaccharides Blend Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03722550
Recruitment Status : Recruiting
First Posted : October 29, 2018
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Nestlé

Brief Summary:

The aim of this trial is to show that infants fed these new formulas, containing a blend of 5 Human Milk Oligosaccharides (HMOs), allow for growth in line with infants fed formulas without HMOs.

There will be different groups in the trial: three formula-fed groups and a breastfed group.


Condition or disease Intervention/treatment Phase
Healthy Infants Other: Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides Other: Breast-feeding Other: Standard Starter Infant Formula, Follow-up Formula, and Growing-up Milk Not Applicable

Detailed Description:
These 5 HMOs are identical to the ones found naturally in human milk. They are natural prebiotics (or complex sugars) with potential health benefits. Prebiotics are natural compounds that help the establishment of beneficial gut bacteria (such as bifidobacteria), while preventing bad bacteria from doing harm. Supplementing diets with certain prebiotics has been shown to be well tolerated in adults and infants and to provide potential benefits.Therefore, the trial also aims to understand if consuming HMOs supplemented formulas could strengthen immunity and prevent common illnesses (for example, respiratory illnesses) in infants and toddlers. Furthermore, stool frequency and consistency will be monitored, so as to evaluate digestive tolerance to the formula.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 570 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Unique coding of the study products
Primary Purpose: Other
Official Title: Growth, Safety and Efficacy of a Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides: a Double-blind, Randomized, Controlled Trial
Actual Study Start Date : September 19, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Control Group
Standard Starter Infant Formula, Standard Follow-up Formula, and Standard Growing-up Milk
Other: Standard Starter Infant Formula, Follow-up Formula, and Growing-up Milk
Standard Study formulas are administered orally, ad libitum, from enrollment until 15 months of age

Experimental: Test Group 1
Starter Infant Formula (same as Control Group) supplemented with 1.5g/L of Human Milk Oligosaccharides, Follow-up Formula (same as Control Group) supplemented with 0.5g/L of Human Milk Oligosaccharides, and Growing-up Milk (same as Control Group) supplemented with 0.4g/L of Human Milk Oligosaccharides
Other: Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides
Study formulas are administered orally, ad libitum, from enrollment until 15 months of age

Experimental: Test Group 2
Starter Infant Formula (same as Control Group) supplemented with 2.5g/L of Human Milk Oligosaccharides, Follow-up Formula (same as Control Group) supplemented with 0.5g/L of Human Milk Oligosaccharides, and Growing-up Milk (same as Control Group) supplemented with 0.4g/L of Human Milk Oligosaccharides
Other: Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides
Study formulas are administered orally, ad libitum, from enrollment until 15 months of age

Active Comparator: Breastfed Group
Non-randomized Breastfed reference group
Other: Breast-feeding
Exclusive Breast-feeding up to 4 months of age




Primary Outcome Measures :
  1. To compare the growth of infants between the groups [ Time Frame: From Study Day 1 to 4 months of age ]
    To compare the growth (weight gain, g/day) of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG)

  2. To compare recurrent incidences of illness of infants between the groups [ Time Frame: From Study Day 1 to 15 months of age ]
    To compare recurrent incidences of illness (specifically lower respiratory tract illnesses including bronchitis/bronchiolitis), of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG)


Secondary Outcome Measures :
  1. Infant illness and infection outcomes [ Time Frame: at different stages of feeding 1st age Infant Formula, 2nd age Follow-up Formula, and 3rd age Growing-up Milk when applicable ]
    Specific parent-reported infant illness symptoms and physician confirmed diagnoses of lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), total respiratory tract infection (TRTI), gastrointestinal infection (GII), ear illness [including: otitis media (OM), ear infection, ear inflammation, and ear pain], and fever will be combined to report infant illness and infection outcomes (Episode, incidence, duration, severity, and recurrence)

  2. Medication use (specifically antimicrobials and antipyretics) [ Time Frame: From enrollment until 15 months of age ]
    Medication type and duration of intake will be combined to report the medication use

  3. Absenteeism: Time away from daycare (infant) or work (parent) [ Time Frame: From enrollment until 15 months of age ]
    Time away from daycare (infant) or work (parent)

  4. Fecal microbiome composition, diversity, community type [ Time Frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants) ]
    Fecal microbiota composition, diversity, and microbiota community type will be assessed using cutting-edge next generation sequencing technology and combined to report the Fecal microbiome

  5. Fecal metabolic profile [ Time Frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants) ]
    Measures of fecal metabolism will be combined to report fecal metabolic profile (fecal pH, fecal organic acids, as well as additional targeted/untargeted metabolomics and cell-based functional assays)

  6. Markers of immune and gut health [ Time Frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants) ]
    Fecal markers of immune and gut health will include secretory immunoglobulin A IgA [total], alpha-1 antitrypsin, and calprotectin.

  7. Blood Markers of immune health [ Time Frame: At 6 months of age ]
    Plasma and peripheral blood mononuclear cells, Extracellular in vivo and ex vivo circulating cytokine levels will be measured in plasma

  8. Gastrointestinal tolerance [ Time Frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants) ]
    Stool patterns (stool frequency and consistency), Gastrointestinal symptoms, Gastrointestinal-related behaviors, and milk intake will be combined to report the gastrointestinal tolerance

  9. Cognitive and behavioral outcomes [ Time Frame: At 15 months of age ]
    Assessment at 15 months through the use of the MacArthur-Bates Communicative Development Inventories (MCDI) and the Early Childhood Behavior Questionnaire (ECBQ), two parent-reported questionnaires that evaluate early language/vocabulary and development of communication skills, that will be combined to report the cognitive and behavioral outcomes

  10. DNA Genotyping of fucosyltransferase 2 and 3 (secretor status) [ Time Frame: At Study Day 60 +/- 5 days ]
    Association between secretor status and illnesses/infections via microbiome modulation will be evaluated.

  11. Breastmilk collection for Human Milk Oligosaccharides profile analysis (breastfeeding mothers only) [ Time Frame: At Study Day 90 +/- 5 days ]
    A small sample of milk (1ml) will be hand pumped, collected in an Eppendorf tube and stored frozen

  12. Anthropometric measurements: Weight [ Time Frame: From enrollment until 15 months of age ]
    Weight measurements in grams to report anthropometric measurements.

  13. Anthropometric measurements: Length [ Time Frame: From enrollment until 15 months of age ]
    Length measurements in centimeters to report anthropometric measurements.

  14. Anthropometric measurements: Head circumference [ Time Frame: From enrollment until 15 months of age ]
    Head circumference measurements in centimeters to report anthropometric measurements.

  15. Anthropometric measurements: BMI [ Time Frame: From enrollment until 15 months of age ]
    BMI measurements in kg/m^2 to report anthropometric measurements.

  16. Anthropometric measurements: World Health Organization (WHO) growth standard calculated z-scores [ Time Frame: From enrollment until 15 months of age ]
    WHO growth standard z-scores including weight-for-age, length-for-age, weight-for-length, head-circumference-for-age, BMI-for-age and weight velocity will be calculated and combined to report anthropometric measurements.

  17. Vital signs: Infant respiration [ Time Frame: From enrollment until 15 months of age ]
    Infant respiration in breaths per minute will also be measured to report vital signs

  18. Vital signs: Heart rate [ Time Frame: From enrollment until 15 months of age ]
    Heart rate in beasts per minute will also be measured to report vital signs

  19. Vital signs: Body temperature [ Time Frame: From enrollment until 15 months of age ]
    Body temperature in Celsius degree will also be measured to report vital signs

  20. Standard adverse events (AEs) reporting for safety assessment [ Time Frame: From the time the informed consent form has been signed at enrollment infant age less than 21 days or 0.75 months through the 2 weeks post-study telephone contact at infant age 464 days ]
    Reported adverse events (AEs) and Serious Adverse Events (SAEs) include type, incidence, severity, seriousness and relation to feeding



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 21 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s)/Legally Acceptable Representative has been informed of all pertinent aspects of the study.
  2. Infants whose parent(s)/Legally Acceptable Representative have reached the legal age of majority in the countries where the study is conducted.
  3. Infants whose parent(s)/Legally Acceptable Representative are willing and able to comply with scheduled visits, and the requirements of the study protocol.
  4. Infants whose parent(s)/Legally Acceptable Representative are able to be contacted directly by telephone throughout the study.
  5. Infants whose parent(s)/Legally Acceptable Representative have a working freezer.
  6. Infants must meet all of the following inclusion criteria to be eligible for enrollment into the study:

    1. Healthy term (37-42 weeks of gestation) infant at birth.
    2. At enrollment visit, post-natal age ≥ 7 days and ≤ 21 days (date of birth = day 0, 0.25 - 0.75 months old).
    3. At enrollment, birth weight ≥ 2500g and ≤ 4500g.
    4. For formula-fed group, infants must be exclusively consuming and tolerating a cow's milk infant formula at time of enrollment and their parent(s)/Legally Acceptable Representative must have independently elected, before enrollment, not to breastfeed.
    5. For breastfed group, infants must have been exclusively consuming breast milk since birth, and their parent(s)/Legally Acceptable Representative must have made the decision to continue exclusively breastfeeding until at least 4 month of age.

Exclusion Criteria:

  1. Infants with conditions requiring infant feedings other than those specified in the protocol.
  2. Infants receiving complementary foods or liquids defined as 4 or more teaspoons per day or approximately 20 g per day of complementary foods or liquids at or prior to enrollment.
  3. Infants who have a medical condition or history that could increase the risk associated with study participation or interfere with the interpretation of study results, including:

    1. Evidence of major congenital malformations (e.g., cleft palate, extremity malformation).
    2. Suspected or documented systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis).
    3. History of admission to the Neonatal Intensive Care Unit (NICU), with the exception of admission for jaundice phototherapy.
    4. Other severe medical or laboratory abnormality (acute or chronic) which, in the judgment of the investigator, would make the infant inappropriate for entry into the study.
  4. Infants who are presently receiving or have received prior to enrollment any of the following: medication(s) or supplement(s) which are known or suspected to affect the following: fat digestion, absorption, and/or metabolism (e.g., pancreatic enzymes); stool characteristics (e.g., glycerin suppositories, bismuth-containing medications, docusate, Maltsupex, or lactulose); growth (e.g. insulin or growth hormone); gastric acid secretion; or any study outcomes.
  5. Currently participating or having participated in another clinical trial since birth

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722550


Contacts
Layout table for location contacts
Contact: Sebastien Paoli +41797111417 sebastien.paoli@rdls.nestle.com
Contact: Aude Chevalier +41217858293 Aude.Chevalier@rdls.nestle.com

Locations
Show Show 31 study locations
Sponsors and Collaborators
Nestlé
Investigators
Layout table for investigator information
Principal Investigator: Aleksander Krasnow, Lek. Med. Gdańskie Centrum Zdrowia Sp. Z o.o.
Principal Investigator: Wiesław Olechowski, Dr n.med. ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. Z o.o.
Principal Investigator: Sylwia Korzyńska, MD Centrum Medyczne Pratia Ostrolęka
Principal Investigator: Anna Płoszczuk, Dr. n.med. Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny Anna Płoszczuk
Principal Investigator: Magdalena Sidorowicz, Dr. Centrum Medyczne Pratia Warszawa
Principal Investigator: Grażyna Jasieniak-Pinis, Lek. Med. ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne
Principal Investigator: Bartosz Korczowski, PhD MD Dr Korczowski Bartosz Gabinet Lekarski
Principal Investigator: Piotr Korbal, Dr. Szpital Uniwersytecki nr 2 Im. Dr Jana Biziela w Bydgoszczy Oddział Kliniczny Noworodków, Wcześniaków z Intensywną Terapią Noworodka wraz z
Principal Investigator: Marta Żołnowska, Lek. Med. Centrum Medyczne Plejady
Principal Investigator: Bogusław Cimoszko, Lek. Med. Clinical Vitae Sp z o.o. Poradnia Podstawowej Opieki Zdrowotnej
Principal Investigator: Wanda Furmaga-Jabłonska, Prof. Uniwersytecki Szpital Dziecięcy w Lublinie
Principal Investigator: Marzena Nowak, Dr. Centrum Medyczne PROMED
Principal Investigator: Georgios Marek Vasilopoulos, Dr. Centrum Innowacyjnych Terapii Sp. z o.o.
Principal Investigator: Viktor Bauer, MD Dr. Kenessey Albert Kórház-Rendelőintézet
Principal Investigator: Robert Simkó, MD Futurenest Kft.
Principal Investigator: István Laki, MD Kanizsai Dorottya Kórház
Principal Investigator: Éva Kovács, MD Házi Gyermekorvosi Rendelő / Babadoki Kft.
Principal Investigator: Éva Szabó, MD Csolnoky Ferenc Kórház
Principal Investigator: István Tokodi, MD Mentaház Magánorvosi Központ Kft.
Principal Investigator: Zsuzsanna Tengelyi, MD Clinexpert Kft.
Principal Investigator: Katalin Fister, MD Clinexpert Gyöngyös Egészségügyi Szolgáltató Kft.
Principal Investigator: Anton Bilev, MD MC ''Sveti Ivan Rilski - Chudotvorets''
Principal Investigator: Miroslava Bosheva, MD University Multiorofile Hospital for active treatment Sveti Georgi EAD, Pediatric clinic
Principal Investigator: Toni Grigorov, MD Multiprofile Hospital for Active Treatment City Clinic - Sveti Georgi EOOD,Department of Paediatrics,
Principal Investigator: Rositsa Karcheva-Beloeva, MD Medical Center-1-Sevlievo
Principal Investigator: Margarita Koleva, MD Diagnostic-consultative center Ritam TR
Principal Investigator: Stelyana Kraeva, MD Alitera -Med-Medical Center
Principal Investigator: Olga Nikolova, MD Multiprofile Hospital for Active Treatment Sveti Ivan Rilski Kozloduy,Department of Pediatrics
Principal Investigator: Tatyana Stoeva, MD Medical Centre - Izgrev
Principal Investigator: Maria Tarneva, MD University Hospital 'Deva Maria', Department for Naonatology
Principal Investigator: Svilen Dosev, MD Multiprofile Hospital for Active treatment Ruse AD, Department of Paediatrics

Layout table for additonal information
Responsible Party: Nestlé
ClinicalTrials.gov Identifier: NCT03722550    
Other Study ID Numbers: 1624INF
First Posted: October 29, 2018    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No