Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group | Active Comparator | Standard Starter Infant Formula, Standard Follow-up Formula, and Standard Growing-up Milk |
|
| Test Group 1 | Experimental | 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 |
|
| Test Group 2 | Experimental | 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 |
|
| Breastfed Group | Active Comparator | Non-randomized Breastfed reference group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides | Other | Study formulas are administered orally, ad libitum, from enrollment until 15 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the growth of infants between the groups | To compare the growth (weight gain, g/day) of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG) | From Study Day 1 to 4 months of age |
| To compare recurrent incidences of illness of infants between the groups | To compare recurrent incidences of illness (specifically lower and upper respiratory tract illnesses including bronchitis/bronchiolitis), of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG) | From Study Day 1 to 15 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| Infant illness and infection outcomes | 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) |
Not provided
Inclusion Criteria:
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.
Infants whose parent(s)/Legally Acceptable Representative have reached the legal age of majority in the countries where the study is conducted.
Infants whose parent(s)/Legally Acceptable Representative are willing and able to comply with scheduled visits, and the requirements of the study protocol.
Infants whose parent(s)/Legally Acceptable Representative are able to be contacted directly by telephone throughout the study.
Infants whose parent(s)/Legally Acceptable Representative have a working freezer.
Infants must meet all of the following inclusion criteria to be eligible for enrollment into the study:
Exclusion Criteria:
Infants with conditions requiring infant feedings other than those specified in the protocol.
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.
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:
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.
Currently participating or having participated in another clinical trial since birth
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sveti Ivan Rilski - Chudotvorets | Blagoevgrad | 2700 | Bulgaria | |||
| University Hospital Deva Maria, Department for Naonatology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35873420 | Derived | Bosheva M, Tokodi I, Krasnow A, Pedersen HK, Lukjancenko O, Eklund AC, Grathwohl D, Sprenger N, Berger B, Cercamondi CI; 5 HMO Study Investigator Consortium. Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial. Front Nutr. 2022 Jul 6;9:920362. doi: 10.3389/fnut.2022.920362. eCollection 2022. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Unique coding of the study products
| Breast-feeding | Other | Exclusive Breast-feeding up to 4 months of age |
|
| Standard Starter Infant Formula, Follow-up Formula, and Growing-up Milk | Other | Standard Study formulas are administered orally, ad libitum, from enrollment until 15 months of age |
|
| at different stages of feeding 1st age Infant Formula, 2nd age Follow-up Formula, and 3rd age Growing-up Milk when applicable |
| Medication use (specifically antimicrobials and antipyretics) | Medication type and duration of intake will be combined to report the medication use | From enrollment until 15 months of age |
| Absenteeism: Time away from daycare (infant) or work (parent) | Time away from daycare (infant) or work (parent) | From enrollment until 15 months of age |
| Fecal microbiome composition, diversity, community type | 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 | 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 metabolic profile | 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) | 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) |
| Markers of immune and gut health | Fecal markers of immune and gut health will include secretory immunoglobulin A IgA [total], alpha-1 antitrypsin, and calprotectin. | 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) |
| Blood Markers of immune health | Plasma and peripheral blood mononuclear cells, Extracellular in vivo and ex vivo circulating cytokine levels will be measured in plasma | At 6 months of age |
| Gastrointestinal tolerance | Stool patterns (stool frequency and consistency), Gastrointestinal symptoms, Gastrointestinal-related behaviors, and milk intake will be combined to report the gastrointestinal tolerance | 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) |
| Cognitive and behavioral outcomes | 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 | At 15 months of age |
| DNA Genotyping of fucosyltransferase 2 and 3 (secretor status) | Association between secretor status and illnesses/infections via microbiome modulation will be evaluated. | At Study Day 60 +/- 5 days |
| Breastmilk collection for Human Milk Oligosaccharides profile analysis (breastfeeding mothers only) | A small sample of milk (1ml) will be hand pumped, collected in an Eppendorf tube and stored frozen | At Study Day 90 +/- 5 days |
| Anthropometric measurements: Weight | Weight measurements in grams to report anthropometric measurements. | From enrollment until 15 months of age |
| Anthropometric measurements: Length | Length measurements in centimeters to report anthropometric measurements. | From enrollment until 15 months of age |
| Anthropometric measurements: Head circumference | Head circumference measurements in centimeters to report anthropometric measurements. | From enrollment until 15 months of age |
| Anthropometric measurements: BMI | BMI measurements in kg/m^2 to report anthropometric measurements. | From enrollment until 15 months of age |
| Anthropometric measurements: World Health Organization (WHO) growth standard calculated z-scores | 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. | From enrollment until 15 months of age |
| Vital signs: Infant respiration | Infant respiration in breaths per minute will also be measured to report vital signs | From enrollment until 15 months of age |
| Vital signs: Heart rate | Heart rate in beasts per minute will also be measured to report vital signs | From enrollment until 15 months of age |
| Vital signs: Body temperature | Body temperature in Celsius degree will also be measured to report vital signs | From enrollment until 15 months of age |
| 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 21 days or 0.75 months through the 2 weeks post-study telephone contact at infant age 464 days |
| Bone index measurement | Bone index measurement will be conducted using a non-invasive and radiation-free ultra-sound sonometer measuring bone transmission time and speed of sound at the radius and tibia site, including also the measurement of the femur and radius length | From enrollment until 15 months of age |
| Dietary pattern | Dietary pattern will be evaluated using a Food frequency questionnaire including sixteen key food groups for infants and young children | From 6 months of age until 15 months of age |
| 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 |
| Irina Popova, MD | University Hospital 'Deva Maria', Department for Naonatology | Principal Investigator |
| Svilen Dosev, MD | Multiprofile Hospital for Active treatment Ruse AD, Department of Paediatrics | Principal Investigator |
| Stefan Banov, MD | SMA Dr Stefan Banov | Principal Investigator |
| Sirma Dimitrova, MD | Medical Center Excelsior | Principal Investigator |
| Malgorzata Arciszewska, MD | Poliklinika Ginekolo.-Poloznicza | Principal Investigator |
| Burgas |
| 8000 |
| Bulgaria |
| Multiprofile Hospital for Active Treatment Sveti Ivan Rilski Kozloduy,Department of Pediatrics | Kozloduy | 3320 | Bulgaria |
| Multiprofile Hospital for Active Treatment City Clinic - Sveti Georgi EOOD,Department of Paediatrics | Montana | 3400 | Bulgaria |
| University Multiorofile Hospital for active treatment Sveti Georgi EAD, Pediatric clinic | Plovdiv | 4002 | Bulgaria |
| Multiprofile Hospital for Active treatment- Ruse AD, Department of Paediatrics | Rousse | 7000 | Bulgaria |
| Medical Center-1-Sevlievo EOOD | Sevlievo | 5400 | Bulgaria |
| 1st Pediatric Consultative Clinic | Sofia | 1404 | Bulgaria |
| Medical Center Excelsior | Sofia | 1407 | Bulgaria |
| Medical Centre - Izgrev EOOD | Sofia | 1612 | Bulgaria |
| Alitera-Med-Medical Center EOOD | Sofia | 1618 | Bulgaria |
| Diagnostic-consultative center Ritam TR'' OOD | Stara Zagora | 6000 | Bulgaria |
| SMA Dr Stefan Banov | Stara Zagora | 6000 | Bulgaria |
| Dr. Kenessey Albert Kórház-Rendelőintézet Csecsemő és Gyermekosztály | Balassagyarmat | 2660 | Hungary |
| Clinexpert Kft. | Budapest | 1033 | Hungary |
| Clinexpert Gyöngyös Egészségügyi Szolgáltató Kft. | Gyöngyös | 3200 | Hungary |
| Futurenest Kft. | Miskolc | 3527 | Hungary |
| Kanizsai Dorottya Kórház Csecsemő és Gyermekgyógyászati Osztály | Nagykanizsa | 8800 | Hungary |
| Házi Gyermekorvosi Rendelő / Babadoki Kft. | Szeged | 6723 | Hungary |
| Mentaház Magánorvosi Központ Kft. | Székesfehérvár | 8000 | Hungary |
| Csolnoky Ferenc Kórház | Veszprém | 8200 | Hungary |
| Poliklinika Ginekolo.-Poloznicza | Bialystok | 15-435 | Poland |
| Szpital Uniwersytecki nr 2 | Bydgoszcz | 85-168 | Poland |
| Clinical Vitae Sp z o.o. Poradnia Podstawowej Opieki Zdrowotnej | Gdansk | 80-180 | Poland |
| Gdańskie Centrum Zdrowia Sp. Z o.o | Gdansk | 80-542 | Poland |
| Centrum Medyczne Plejady | Krakow | 30-363 | Poland |
| Grażyna Jasieniak-Pinis ATOPIA Niepubliczny Zakład Opieki Zdrowotnej Poradnie Specjalistyczne | Krakow | 31-159 | Poland |
| Centrum Medyczne PROMED | Krakow | 31-411 | Poland |
| Uniwersytecki Szpital Dziecięcy w Lublinie | Lublin | 20-093 | Poland |
| Centrum Medyczne Pratia Ostrolęka | Ostrołęka | 07-410 | Poland |
| Centrum Innowacyjnych Terapii Sp. z o.o. | Piaseczno | 05-500 | Poland |
| Korczowski Bartosz Gabinet Lekarski | Rzeszów | 35-302 | Poland |
| ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. Z o.o | Tarnów | 33-100 | Poland |
| Centrum Medyczne Pratia Warszawa | Warsaw | 01-868 | Poland |
| ID | Term |
|---|---|
| D007774 | Lactation |
| ID | Term |
|---|---|
| D055703 | Reproductive Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
| D049590 | Postpartum Period |
Not provided
Not provided