Effects of Probiotics and Calcium Supplementation on Growth, Development, and Metabolic Parameters

Completed

• Conditions: Permeability; Increased; Cognitive Function 1, Social; Behavior; Insulin Resistance; Stunting; Dyslipidemias; Obesity; Depression
• Interventions: Dietary Supplement: Low Calcium Milk; Dietary Supplement: Probiotic 2; Dietary Supplement: Regular Calcium Milk; Dietary Supplement: Probiotic 1

• Registration Number: NCT04046289
• Lead Sponsor: Indonesia University

Brief Summary

Stunting is still a major problem in developing countries, including Indonesia, and has been associated with impaired development. Stunted children have also a higher risk of metabolic syndrome in adulthood. The gut microbiota, as a part of intestinal integrity, may promote intake of nutrient during childhood. Probiotics supplementation may optimize the balance of gut microbiota and further improve child growth during the window period. Furthermore, calcium could also improve child growth by increasing the resistance to intestinal infection. However, the long-term effects of gut microbiota optimization during childhood using probiotics and calcium on growth, development, and the metabolic condition has not widely studied.

Detailed Description

This study was a 10-year follow-up study of randomized controlled trials of 6-month probiotics and calcium supplementation of Lactobacillus reuteri DSM 17938 or Lactobacillus casei CRL 431 in children aged 1-6 years (n=494) living in urban low socioeconomic communities of East Jakarta in 2007-2008. We re-enrolled the subjects to assess the long-term effects of probiotics and calcium supplementation on growth, development, and metabolic parameters at the age of 11-17 years.

Healthy children (n = 238) were included in this follow-up study. Each subject previously assigned to one intervention group: low-lactose milk with a low calcium content (LC = 53), a regular calcium content (RC = 70), regular calcium with L. reuteri DSM 17938 (n = 55), and regular calcium with L. casei CRL 431 (n = 60).

Anthropometric measurements were performed by measuring the weight and height of the subjects, and further combining the results to report BMI-for-age z-score. Height was also plotted to the chart of the World Health Organization (WHO) Child Growth Standards. Gut integrity was assessed with the lactulose-mannitol ratio using high-performance liquid chromatography (HPLC) method. Cognitive function, symptoms related to depression, behaviour, and serum brain-derived neurotrophic factors (BDNF) of the adolescents were evaluated used to investigate the effects of supplementation on development. We quantified lipid profile and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as metabolic parameters using the vein blood sample. The metabolic parameters were measured in at least three groups of intervention.

Study Timeline

• Study Start: 2019-01-26
• Primary Completion: 2019-03-03
• Study Completion: 2019-07-05
• Status Verified: 2019-08
• Study First Submitted: 2019-08-01
• Study First Submitted QC: 2019-08-02
• Last Update Submitted: 2019-08-05
• Study First Posted: 2019-08-06
• Last Update Posted: 2019-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 238

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Low Calcium	Low Calcium Milk	low calcium milk of 180 ml, twice daily for 24 weeks
Probiotic 2	Probiotic 2	regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks
Regular Calcium	Regular Calcium Milk	regular calcium milk of 180 ml, twice daily for 24 weeks
Probiotic 1	Probiotic 1	regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
Child's linear growth the age of 11-17 years	January - March 2019	Height-for-age z-score based on the WHO Child Growth Standards.
Child's height at the age of 11-17 years	January - March 2019	Height in meters.
Child's weight at the age of 11-17 years	January - March 2019	Weight in kilograms.
Child's nutritional status at the age of 11-17 years	January - March 2019	BMI-for-age z-score based on the WHO Child Growth Standards. BMI was calculated from height and weight measurement.

Secondary Outcome Measures

Name	Time	Method
Gut integrity at the age of 11-17 years	January - March 2019	Lactulose-mannitol ratio was calculated by dividing percent excretion of lactulose with percent excretion of mannitol.
Cognitive function assessed using Raven's Progressive Matrices at the age of 11-17 years	January - March 2019	Raven's Progressive Matrices (RPM) was administered by psychologists. Raw score of RPM was used to evaluate adolescents' cognition.
Symptoms related to depression assessed using Children Depression Inventory at the age of 11-17 years	January - March 2019	Children Depression Inventory (CDI) was a self-assigned questionnaire and the total score of CDI with a range between 0 - 54 (lower, better) was used to evaluate the symptoms related to depression among adolescents.
Behaviour assessed using Strength and Difficulties Questionnaire at the age of 11-17 years	January - March 2019	Strength and Difficulties Questionnaire (SDQ) was a self-assigned questionnaire and the total difficulties score of SDQ with a range between 0 - 50 (lower, better) was used to evaluate the behaviour among adolescents.
Serum BDNF at the age of 11-17 years	January - March 2019	Serum BDNF in pg/ml was quantified using ELISA method
Triglyceride level at the age of 11-17 years	January - March 2019	Triglyceride level in milligrams per decilitre.
Low-density lipoprotein level at the age of 11-17 years	January - March 2019	Low-density lipoprotein level in milligrams per decilitre.
Fasting glucose level at the age of 11-17 years	January - March 2019	Fasting glucose level in milligrams per decilitre.
HOMA-IR at the age of 11-17 years	January - March 2019	HOMA-IR was quantified by multiplying fasting insulin level with fasting glucose level.
High-density lipoprotein level at the age of 11-17 years	January - March 2019	High-density lipoprotein level in milligrams per decilitre.
Fasting insulin level at the age of 11-17 years	January - March 2019	Fasting insulin level in μU per millilitre

Trial Locations

Locations (1)

Human Nutrition Research Center, Indonesian Medical Education Research Institute; and Department of Nutrition, Faculty of Medicine, Universitas Indonesia; 🇮🇩 Jakarta Pusat, DKI Jakarta, Indonesia