Ingestion Effect of Formula Milk With Triple Bifidobacteria Strains on Fecal Quality and Metabolites in Healthy Children

NCT06044376 | Unknown Phase 1

• 1 other identifier: PUIPTProbiotikUGM_P002
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 10

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. 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. 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. 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)?

Conditions

Children, Only

Keywords

Children; Fecal sample; Triple Bifidobacterium strains; Probiotic; Formula milk; Indonesia

Outcome Measures

Primary Outcomes (7)

• Fecal characteristics

  Observed the shape, color and consistency of fecal samples that will be combined to be reported as fecal type according to the Bristol Stool Chart

  Before and after intervention period (day 13 and day 105)

• Fecal pH

  The pH of obtained fecal samples were measured using potential of hydrogen (pH) meter

  Before and after intervention period (day 13 and day 105)

• Bacterial colony characteristics

  From the fecal samples obtained, direct plating using the selective media for Bifidobacterium (Bifidobacterium Selective Medium or BSM) and Enterobacteriaceae (MacConkey Agar) is conducted. Colony bacterial characterization is based on the cell morphology and Gram strain characteristics under the microscope.

  Before and after intervention period (day 13 and day 105)

• Bifidobacterium's cell count

  The cell number is a total of Bifidobacteria cells obtained from DNA extraction of stool samples counted using quantitative PCR (qPCR). Cell count will be expressed in colony forming unit per gram (CFU/g).

  Before and after intervention period (day 13 and day 105)

• Enterobactericaeae's cell count

  The cell number is a total of Enterobacteriaceae's cells obtained from DNA extraction of stool samples counted using quantitative PCR (qPCR). Cell count will be expressed in colony forming unit per gram (CFU/g)

  Before and after intervention period (day 13 and day 105)

• Short chain fatty acids analysis

  The analysis includes the measurement of acetate, propionate, and butyrate. The analysis uses gas chromatography method.

  Before and after intervention period (day 13 and day 105)

• Biomarker of immune systems

  The analysis on immune systems' biomarker uses the fecal water obtained from diluting the fecal samples into phosphate buffer. The fecal water is then added with protease inhibitor to keep fecal samples stable during the analysis. The immune system analyzed are interleukin 6 (IL6), interleukin 8 (IL8), interleukin 10 (IL10) and secretory immunoglobulin A (SIgA). All immune systems are read using the enzyme-linked Immunosorbent Assay (ELISA) Reader BioRad iMark.

  Before and after intervention period (day 13 and day 105)

Secondary Outcomes (17)

• Defecation frequency records

  Everyday during the research period (104 days)

• Dietary pattern records

  Four days every two weeks, consists of two weekdays and two weekend days during the research period

• Health complaint and medical records

  Everyday during the research period (104 days)

• Health profile record

  Before and after intervention period (day 13 and day 105)

• Gastrointestinal disorder record

  Before and after intervention period (day 13 and day 105)

Study Arms (2)

Probiotic Group

ACTIVE COMPARATOR

During the baseline period, all participants consumed milk formula without any addition of probiotics three servings per day for 14 days. One serving of milk formula consists of 36 gram that is diluted in 180 mL lukewarm water. The participants in the probiotic group consumed milk formula added with triple Bifidobacterium strain containing Bifidobacterium longum BB536 (6.9 x 10\^7 CFU/serving), Bifidobacterium breve M16-V (6.9 x 10\^7 CFU/serving), Bifidobacterium longum subsp. infantis M-63 (6.9 x 10\^7 CFU/serving). The milk formula is consumed three servings per day for 90 days during the intervention period. One serving of milk formula consists of 36 gram that is diluted in 180 mL lukewarm water.

Combination Product: Formula milk with triple Bifidobacterium probiotic strain

Placebo Group

PLACEBO COMPARATOR

During the research period (both baseline and intervention period), all participants consumed milk formula without any addition of probiotics three servings per day for 104 days. One serving of milk formula consists of 36 gram that is diluted in 180 mL lukewarm water.

Other: Formula milk

Interventions

Formula milk with triple Bifidobacterium probiotic strain COMBINATION_PRODUCT

Formula milk with triple Bifidobacterium strain containing Bifidobacterium longum BB536 (6.9 x 10\^7 CFU/serving), Bifidobacterium breve M16-V (6.9 x 10\^7 CFU/serving), Bifidobacterium longum subsp. infantis M-63 (6.9 x 10\^7 CFU/serving).

Probiotic Group

Formula milk OTHER

Formula milk without any addition of probiotic strain

Placebo Group

Eligibility Criteria

• Age: 12 Months - 36 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gadjah Mada University: lead
• PT Kalbe Farma Tbk: collaborator
• Morinaga Milk Industry Co., LTD: collaborator

Study Sites (10)

PAUD Hiber Rotowijayan

Yogyakarta, Special Region of Yogyakarta, 55132, Indonesia

Location

Paud Kunir Ceria Tegalgendu Kotagede

Yogyakarta, Special Region of Yogyakarta, 55172, Indonesia

Location

Puskesmas Mlati 2

Yogyakarta, 55286, Indonesia

Location

Paud Bodeh

Yogyakarta, 55294, Indonesia

Location

Paud Gamping Lor

Yogyakarta, 55294, Indonesia

Location

Paud Matahari Mejing 3

Yogyakarta, 55294, Indonesia

Location

Paud Pereng Dawe

Yogyakarta, 55295, Indonesia

Location

Paud Pereng Kembang

Yogyakarta, 55295, Indonesia

Location

Paud Sembung

Yogyakarta, 55295, Indonesia

Location

Paud Sumber

Yogyakarta, 55295, Indonesia

Location

Study Officials

• Endang Sutriswati Rahayu, Prof. Dr. Ir

  Gadjah Mada University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 21, 2023
• Study Start: May 2, 2023
• Primary Completion: November 9, 2023
• Study Completion: March 31, 2024
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ID (10)