Brain Probiotic and LC-PUFA Intervention for Optimum Early Life

NCT03851120 | Completed Phase 2 DMC

• 1 other identifier: BRAVE
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 1

Brief Summary

Probiotics is suggested to play several roles in promoting health, including alleviating disease symptoms, protection against atopic disease, and modulating the immune system by improving the beneficial gut microbiota colonization. The discovery of the gut microbiota-brain axis suggested that there is a reciprocal influence between the brain and the gut through a constant communication. This bi-directional axis enables signals to be transferred from brain to influence sensory, motor, and secretory modalities of the GI tract, also permits signal from the gut to influence brain function. The establishment of intestinal microbiota during early neurodevelopmental period suggests the colonization and maturation of gut microbiota may influence brain development. Several studies have shown there is an association between shifts in the gut microbiota composition in children with neurodevelopmental disorders. This study aims to investigate how maternal probiotic + LC-PUFA supported with government program supplements, healthy eating, and psychosocial stimulation could affect fetal brain development and later child brain functions and cognitive development. Intervention would be delivered to pregnant women for 9 months, starting at the end of second trimester of gestational period.

Conditions

Maternal Exposure; Health Behavior; Infant Development; Child Development

Outcome Measures

Primary Outcomes (6)

• Total brain volume

  measured in parenchymal and cortical regions

  1 year

• Fetal brain development

  Myelination index

  1 year

• Child cognitive at 4 months of age

  Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); a higher score indicates better performance

  1 year

• Brain function at 4 months of age

  Brainstem Evoked Response Audiometry (BERA)

  1 year

• Eye tracking tasks at 6 months of age

  Visual paired comparison memory task and Infant Orienting with Attention task at 4 months of age

  1 year

• Child cognitive at 6 months of age

  Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); a higher score indicates better performance

  1 year

Secondary Outcomes (36)

• Mother depression scale

  1 year

• Birth weight

  4 month

• Child's Growth

  6 months

• Child's linear growth

  6 months

• Head circumference

  6 months

Study Arms (2)

Intervention

EXPERIMENTAL

150 pregnant women will be given Probiotics and 480 mg DHA, psychosocial stimulation, and healthy eating education

Dietary Supplement: Probiotics and LC-PUFA (480 mg DHA); Behavioral: Psychosocial stimulation and healthy eating education

Control

PLACEBO COMPARATOR

150 pregnant women will be given placebo probiotics and 240 mg DHA, psychosocial stimulation, and healthy eating education

Dietary Supplement: Placebo probiotics and control LC-PUFA (120 mg DHA); Behavioral: Psychosocial stimulation and healthy eating education

Interventions

Probiotics and LC-PUFA (480 mg DHA) DIETARY_SUPPLEMENT

Probiotics and LC-PUFA (480 mg DHA)

Intervention

Placebo probiotics and control LC-PUFA (120 mg DHA) DIETARY_SUPPLEMENT

Placebo probiotics and control LC-PUFA (120 mg DHA)

Control

Psychosocial stimulation and healthy eating education BEHAVIORAL

Psychosocial stimulation and healthy eating education

Control; Intervention

Eligibility Criteria

• Age: 20 Years - 40 Years
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Each pregnant woman must meet all of the following criteria to be enrolled in this study:
• \. Indonesian pregnant women in the 2nd trimester of gestational period 2. healthy pregnancy (as measured by hemoglobin level, pregnancy status, pregnancy history) 3. Having a normal blood pressure 4. Planning to stay in the study area until the child is 6 months old 5. Willing to sign informed consent 5. Having a legally acceptable representative who is capable to understand the informed consent document and providing consent on the subject's behalf

You may not qualify if:

• Each pregnant women meeting any of the following criteria will be excluded from the study:
• Having foreign objects in the body due to trauma, artificial heart value, metal objects or ferromagnetic (plate, screw, clip, prosthetic), and electronic device (pacemaker, cochlear implant, insulin pump), and being claustrophobic
• Having history of previous gestational diabetes or been diagnosed to have gestational diabetes
• Having history of type 1 and type 2 diabetes
• Severe anemia
• Child age above 24 months from the BRAVE intervention project
• Having a legally acceptable representative who is capable to understand the informed consent document and providing consent on the subject's behalf
• \. Child being hospitalized during the study/data collection

Sponsors & Collaborators

• Indonesia University: lead
• Grand Challenges Canada: collaborator

Study Sites (1)

Human Nutrition Research Center, Indonesian Medical Education Research Institute; and Department of Nutrition, Faculty of Medicine, Universitas Indonesia

Jakarta Pusat, DKI Jakarta, 13420, Indonesia

Location

Related Publications (4)

• Sheridan PO, Bindels LB, Saulnier DM, Reid G, Nova E, Holmgren K, O'Toole PW, Bunn J, Delzenne N, Scott KP. Can prebiotics and probiotics improve therapeutic outcomes for undernourished individuals? Gut Microbes. 2014 Jan-Feb;5(1):74-82. doi: 10.4161/gmic.27252. Epub 2013 Dec 16.

  PMID: 24637591 BACKGROUND

• Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The Central Nervous System and the Gut Microbiome. Cell. 2016 Nov 3;167(4):915-932. doi: 10.1016/j.cell.2016.10.027.

  PMID: 27814521 BACKGROUND

• Naaktgeboren, C. Effect of maternal probiotic exposure during pregnancy and lactation on the mother and infant. International Journal of Probiotics and Prebiotics 5: 113-124, 2010

  BACKGROUND

• Ramakrishnan, U. A review of the benefits of nutrients supplements during pregnancy: from iron -folic-acid to long-chain polyunsaturated fatty acids to probiotics. Annales Nestle (English Ed): 29-40, 2010

  BACKGROUND

MeSH Terms

Conditions

Health Behavior

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Rina Agustina, PhD

  Human Nutrition Research Center, IMERI; Dep of Nutrition, Fac.of Medicine UI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, care provider, investigator, and outcomes assessor do not know which one is the intervention product or placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Combination product: Probiotics and LC-PUFA The product will be given to 314 pregnant women, 157 pregnant women as an intervention group, and 157 pregnant women as a control group

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 22, 2019
• Study Start: October 31, 2019
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2024
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)