The BEGIN Study Bifidobacterium Infantis to Newborns: Effects of Modulating the Gut Microbial Composition on Growth, Immune Function and Inflammatory Conditions - a Randomized Placebo-controlled Double-blinded Intervention Trial

Healthy Clinical Trial

— BEGIN  

Official title:

The BEGIN Study Bifidobacterium Infantis to Newborns: Effects of Modulating the Gut Microbial Composition on Growth, Immune Function and Inflammatory Conditions

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06452199
• Other study ID #: BEGIN 2024
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: November 2043

Study information

• Verified date: April 2024
• Source: University of Aarhus
• Contact: Marie T Philipsen, MD, PhD.stud
• Phone: 53637369
• Email: marie.tholstrup[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of The BEGIN Study, a randomized controlled double-blinded intervention trial, is to learn if probiotics, with Bifidobacterium longum subspecies infantis Bifin02 (B. infantis), given to healthy newborns can affect various health outcomes and to explore impacts of the infant gastrointestinal microbiome. The main questions it aims to answer are:

• Does B. infantis probiotics impact immune function and does it lower the number of bacterial infections and use of antibiotics?

• Does B. infantis probiotics impact overall health, development, growth and wellbeing?

• Does B. infantis probiotics impact inflammatory diseases, allergies and autoimmune diseases

Researchers will compare B. infantis probiotics to a placebo (a look-alike substance that contains no probiotic) to see if B. infantis colonization impact the human immunesystem and various clinical and biochemical health markers.

Participants (parents) will

• Orally administrate the B. infantis probiotic to their newborn child daily in three weeks from 7 days of age.

• Answer baseline and follow up questionnaires in a study app

• Take five stool samples from the child and one stool sample from the mother

• Collect a 4 week of passive dust sample at home (Electrostatic Dust fall Collector)

• Donate one dried bloodspot and one blood sample from their child

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1000
• Est. completion date: November 2043
• Est. primary completion date: November 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 7 Days

Eligibility

Inclusion Criteria:

• Infants born at term (above gestational week 37)

• Infants born in Region Midtjylland Denmark receiving a Danish CPR number.

• Parents age is above 18

• At least one parent holds a smartphone (for study app) and is able to fill out Danish questionaries

• Both legal parents are willing and able to provide written informed consent prior to participation, regarding both themselves and their future child.

Exclusion Criteria:

• Multiple pregnancy

• Child diagnosed with immune deficiency, renal, gastrointestinal, hepatic, or endocrine diseases

• Parents expecting to give other probiotics

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• B. infantis
1000 newborn children are randomized 50/50 to receive either B. infanits or placebo in a dietary supplement, for daily oral administration in three weeks from 7 days of age.
• Placebo
Identical looking placebo (without any probiotics/B. infantis) for double-blinded daily oral administration in three weeks from 7 days of age.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Gødstrup Hospital, Regional Hospital Horsens, Statens Serum Institut, Technical University of Denmark, University of Copenhagen

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospital admissions	Number of hospital admissions. Registered at Landspatientregistret	First assessment at 1 year and up to 18 years follow-up
Other	Febrile episodes	Number of days with a fever during the last month. A febrile episode is characterized as a body temperature at 38 degrees Celsius or above. Self-reported in a monthly questionnaire in study app.	1 year
Other	Asthma Control Test	Participants reporting symptoms of astma or astmatic bronkitis, will be asked to complete the Asthma Control Test. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score >19 indicates well-controlled asthma.	1 year, possible later follow-up
Other	Asthmatic Bronchitis, prescriptions	Number of prescriptions of medicine for asthmatic bronchitis; Ventoline, Airomir, Flixotide, Aerobec, Montelukast / Singulair.	First assessment at 1 year
Other	Asthmatic bronchitis, hospitalization	Number of hospitalizations due to asthmatic bronchitis.	First assessment at 1 year
Other	Diaper rash	Atopic skin symptoms in diaper area. Self-reported by the childs parents as affected red skin, distribution in centimeters .	1 year
Other	Rhinoconjunctivitis	Measured as Mini Rhinoconjunctivitis quality of life questionnaire Mini RQLQ, adjusted to infants. 14 questions in five domains (activity limitation, practical problems, nose symptoms, eye symptoms, and non-nose/ eye symptoms), scores for each question is ranging from 0 to 6, with 0 reflecting no affection and 6 reflecting maximum affection.	1 year
Other	Obesity	Measured as number of participants diagnosed with Obesity	18 years
Other	Metabolic syndrome	Measured as number of participants diagnosed with Metabolic syndrome	18 years
Other	Diabetes	Measured as number of participants diagnosed with Diabetes	18 years
Other	Inflammatory bowel disease	Measured as number of participants diagnosed with of Morbus Crohn and/or Colitis Ulcerosa.	18 years
Other	Dried blood spot for metabolomics	The metabolomic method measures and compares large numbers of metabolites (for example shot chained fatty acids) present in the dried blood sample.	3 months and 1 year
Other	Bloodsample analyzed with Singlecell PBMC method	Single cell sequencing is a method profiling the peripheral blood mononuclear cells (PBMC), by isolating memory B, T and B-cells	1 year
Other	Child stool sample	Stool samples collected at week 1, 4, 13, 28 and 52 will by qPCR or shutgun metagenomics examine the gut microbiome.	1 year
Other	Mother stool sample	A stool sample from the pregnant mother, preferably prior to or during birth. To analyze mothers microbial colonization, that may be transferred to the child, e.g during vaginal birth.	1 month
Other	Mother HMO-secretor status	The type of Human Milk Oligosaccharides (HMO) section in mothers' breastmilk, will be determined to exploratively study the relationship between types of HMO's, mothers HMO-secretor status and effects of B.infantis.	1 month
Other	Asthma	Number of participants with prescriptions of medicine for asthma	up to 18 years follow-up
Other	Atopic disease (adjusted SCORAD grading)	Atopic symptoms, eczema, registered in study-app with description of episodes of atopic dermatitis (adjusted SCORAD grading). Disease intensity is calculated based on six characteristics: erythema, edema, oozing/crusts, excoriations, lichenification, and dryness. Each characteristic is given a score between 0 and 3, where 0 is absent and 3 is severe. The scores for each characteristic are added together for a total intensity score of up to 18.	First assessment at 1 year
Other	Atopic disease, local steroids	Number of participants with prescriptions of local steroids to treat eczema.	First assessment at 1 year and up to 18 years follow-up
Primary	Prescriptions of antibiotics	Number of prescriptions of antibiotics among participants, as a measure of bacterial infections.	First assessment at 1 year and up to 18 years follow-up
Secondary	The intestinal microbiota and B. infantis colonization	Stool samples collected during the first year of life and tested with shutgun metagenomics, assessing the microbial composition..	1 year
Secondary	Antibiotic resistance genes (ARGs)	Amount of Antibiotic resistance genes (ARGs) in participants microbial community in stool samples. Identification with shutgun metagenomics. Assessing the microbial composition and diversity.	1 year
Secondary	Colic	Parents' observations registered in study app. Duration of crying in the first three months of life. Defined as Wessels criteria: Crying for three or more hours a day, three or more days a week, for three or more weeks.	3 months
Secondary	Bowel function, stool consistency	Parents' observations registered in study app, related to their infant child's stool consistency measured at the Infant Stool Scale	3 months
Secondary	Bowel function, stool frequency.	Parents' observations of their infant child's frequency of stool passings, registered in study app	3 months
Secondary	Bowel function, laxatives	Parents' reported use of medical laxatives for their infant child, registered in study app and reported as amount of days using the laxative.	3 months
Secondary	High sensitive C-reactive protein (hs-CRP)	Blood biomarker: Low-grade systemic inflammation. Unit of measurement: mg/l	1 year
Secondary	Cluster of Differentiation 163" (CD163)	Blood biomarker: Macrophage-mediated inflammation and insulin-sensitivity. Unit of measurement: mg/l	1 year
Secondary	Plasma Calprotectin	Blood biomarker: Intestinal inflammation. Unit of measurement: µg/l	1 year
Secondary	Allergies, Immunoglobulin E (IgE)	Blood marker: Allergies. Specific IgE against the 11 most common inhalation allergens and IgE directed against Egg white, cow's milk, codfish, wheat, peanut and soybean. Unit of measurement: IU/l	1 year
Secondary	Allergies	Self reported allergy symptoms	1 year
Secondary	Growth, weight gain	Measured as weight gain in kilograms	First assessment at 1 year and up to 18 years follow-up
Secondary	Growth	Growth velocity and weight-for-length z-scores, measured in kilograms and centimeters and combined for Z-scores.	First assessment at 1 year and up to 18 years follow-up
Secondary	Growth, IGF-1 (Insulin-like Growth Factor-1)	Blood biomarker: Mediating the growth-promoting effects of growth hormone. Unit of measurement: µg/l	1 year
Secondary	Body composition	Measured by air displacement plethysmography (ADP) (Pea Pod) estimating body fat	3 months
Secondary	Body composition	Measured by air displacement plethysmography (ADP) (Pea Pod) estimating muscle mass.	3 months

External Links

•   studywebsite for participants