Clinical trial NCT06044376: Ingestion Effect of Formula Milk With Triple Bifidobacteria Strains on Fecal Quality and Metabolites in Healthy Children
Official title: The Consumption Effect of Formula Milk With Triple Bifidobacteria Strains (Bifidobacterium Longum BB536, Bifidobacterium Breve M-16V, and Bifidobacterium Longum Subsp. Infantis M-63) on Fecal Quality and Metabolites in Healthy Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Children, Only
Keywords: Children
Fecal sample
Triple Bifidobacterium strains
Probiotic
Formula milk
Indonesia
Lead sponsor: Gadjah Mada University
Sponsor class: OTHER
Collaborators: name: PT Kalbe Farma Tbk
name: Morinaga Milk Industry Co., LTD
First posted: 2023-09-21
Enrollment: 103
Sex: ALL
Minimum age (years): 12
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to compare healthy children between 1 to 3 years old. The main question it aims to answer is

1. Is there an effect towards fecal quality after consuming milk formula supplemented with the triple Bifidobacteria strains (Bifidobacterium longum BB536, Bifidobacterium breve M-16V, and Bifidobacterium longum subsp. infantis M-63)?
2. Is there an effect towards short-chain fatty acid composition after consuming milk formula supplemented with the triple Bifidobacteria strains (Bifidobacterium longum BB536, Bifidobacterium breve M-16V, and Bifidobacterium longum subsp. infantis M-63)?
3. Is there an effect towards clinical profile after consuming milk formula supplemented with the triple Bifidobacteria strains (Bifidobacterium longum BB536, Bifidobacterium breve M-16V, and Bifidobacterium longum subsp. infantis M-63)?

The clinical trial period started off with all the participants consuming a milk formula three times a day, for 14 days as a baseline period. Afterwards, the participants were randomly assigned to one of two groups: probiotic and placebo. Following the baseline period, participants in the probiotic group consumed formulated milk supplemented with the triple Bifidobacteria strains, while the placebo group ingested the same formulated milk without adding triple Bifidobacteria strains for 90 days.

Researchers will compare the probiotic and placebo groups to see if there are any effects towards the fecal quality, short-chain fatty acid level and clinical profile after consuming the milk formula.

Detailed description: This clinical trial is a study of 3 strains of Bifidobacterium was conducted in infants aged 1-3 years in Indonesia. The general objective of this study was to determine the benefits of combined supplementation of Bifidobacteria strains (B. longum BB536, B. breve M-16V, and B. longum subsp. infantis M-63) in healthy children aged 1-3 years. The study is conducted for 104 days with a baseline period of 14 days and continued with an intervention period of 90 days. Participants is divided into two groups, which are the intervention group and the placebo group. The study will be conducted using a double-blind randomized, placebo-controlled trial design. A total of 100 participants will be selected based on inclusion and exclusion criteria.

During the screening period (day 0), socialization of the research and signing of informed consent will be carried out for participants who are willing to participate. Participants were asked not to consume fermented milk products, probiotics and prebiotic fortified food/drinks while participating in research activities.

During the baseline period (Day 14), the participants were asked to consume control milk and, represented by their parents, were also asked to fill out research diaries in the form of diet records, records of probiotic products and prebiotic fortified food/drinks consumed, type and frequency of bowel movements, health complaints felt (discomfort, headaches, stomachaches, respiratory tract-related illnesses and fever), medication consumption records, days where the participants refused to eat. Participants were asked to collect research documents and collect stool samples on day 14 +/- 1.

During the intervention period, from day 15 to day 104, participants consumed 36 grams of the test product or placebo dissolved in 180 ml per serving with a consumption frequency of 3 times per day. Product consumption will be recorded in the product consumption logbook and on the subject's diary record form. Once every 2 weeks a health profile measurement (weight, height, arm circumference, head circumference, skinfold thickness) and sleep quality will be measured. Participants were asked to collect research documents and stool samples on day 104 +/- 1 with the same procedure as in the baseline period.

Eligibility criteria: Inclusion Criteria:

* Age between 12 - 36 months
* Normal nutritional status (z-score height-for-age or z-score weight-for-height: -2 SD \< X \< 2 SD)
* Has no dairy allergies
* Does not consume breastmilk anymore during the intervention period
* Willing to participate through the whole research period
* Obtain consent from parents or guardians by signing the informed consent form

Exclusion Criteria:

* Has a history of lactose intolerance, congenital and chronic diseases including irritable bowel syndrome, etc.
* Receive antibiotic or other probiotic supplementation during the 14 day of baseline period.

Primary outcomes:
measure: Fecal characteristics
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Fecal pH
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Bacterial colony characteristics
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Bifidobacterium's cell count
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Enterobactericaeae's cell count
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Short chain fatty acids analysis
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Biomarker of immune systems
timeFrame: Before and after intervention period (day 13 and day 105)
Secondary outcomes:
measure: Defecation frequency records
timeFrame: Everyday during the research period (104 days)
measure: Dietary pattern records
timeFrame: Four days every two weeks, consists of two weekdays and two weekend days during the research period
measure: Health complaint and medical records
timeFrame: Everyday during the research period (104 days)
measure: Health profile record
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Gastrointestinal disorder record
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Sleep quality
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Behaviour assesment
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Development screening
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Psychosocial problems
timeFrame: Before and after intervention period (day 13 and day 105)
measure: Weight
timeFrame: Once every two weeks for 105 days
measure: Height
timeFrame: Once every two weeks for 105 days
measure: Body Mass Index (BMI)
timeFrame: Once every two weeks for 105 days
measure: Arm circumference
timeFrame: Once every two weeks for 105 days
measure: Head circumference
timeFrame: Once every two weeks for 105 days
measure: Subcutaneous fat thickness
timeFrame: Once every two weeks for 105 days
measure: Triceps thickness
timeFrame: Once every two weeks for 105 days
measure: Medical check up
timeFrame: Once every two weeks for 105 days
Other outcomes:
Locations:
city: Yogyakarta
country: Indonesia
facility: PAUD Hiber Rotowijayan
state: Special Region Of Yogyakarta
city: Yogyakarta
country: Indonesia
facility: Paud Kunir Ceria Tegalgendu Kotagede
state: Special Region Of Yogyakarta
city: Yogyakarta
country: Indonesia
facility: Puskesmas Mlati 2
city: Yogyakarta
country: Indonesia
facility: Paud Bodeh
city: Yogyakarta
country: Indonesia
facility: Paud Gamping Lor
city: Yogyakarta
country: Indonesia
facility: Paud Matahari Mejing 3
city: Yogyakarta
country: Indonesia
facility: Paud Pereng Dawe
city: Yogyakarta
country: Indonesia
facility: Paud Pereng Kembang
city: Yogyakarta
country: Indonesia
facility: Paud Sembung
city: Yogyakarta
country: Indonesia
facility: Paud Sumber
Study officials:
affiliation: Gadjah Mada University
name: Endang Sutriswati Rahayu, Prof. Dr. Ir
role: PRINCIPAL_INVESTIGATOR
References: