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

Obesity Clinical Trial

— PROBIOCAL  

Official title:

Effects of 6-Month Probiotics and Calcium Supplementation During Childhood on Growth, Development, and Metabolic Parameters in Adolescents: A 10-Year Follow-up Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04046289
• Other study ID #: probiocal
• Status: Completed
• Start date: January 26, 2019
• Est. completion date: July 5, 2019

Study information

• Verified date: August 2019
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: July 5, 2019
• Est. primary completion date: March 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 11 Years to 17 Years

Eligibility

Inclusion Criteria at the previous clinical trial:

• Apparently healthy children aged 1-6 years, with emphasize on aged 2-5 years, living permanently in low socio-economic urban areas of East Jakarta for at least six months

• Parents are willing to sign the informed consent and give the supplements to the children for six months

• Capable and willing to drink liquid milk with a straw (acceptance to be tested at the screening by providing a sample drink and placebo straw to be consumed under supervision for two days)

Exclusion Criteria at the previous clinical trial:

• Calcium intake exceeding 75% of the Recommended Dietary Allowance (RDA) for calcium (<375 mg/d) based on a Food Frequency Questionnaire

• Currently breastfed children

• Siblings of already included children that are living in the same household, except if it is a twin sibling

• Severely malnourished with or without edema (weight-for-height Z-score of <-3.00 SD)

• Symptoms of chronic/congenital diseases and disabilities, suspected Tuberculosis by clinical examination, and/or history of allergic disease.

• Taking (any) antibiotics during 2 weeks prior to the start of the study (children will be included after 3 weeks of last antibiotic intake

• Participation in another clinical trial at the same time or 2 months prior to the start of this study

• Both mothers and other caregivers present in the family are illiterate

Inclusion criteria of follow-up study:

• Healthy adolescent participated in the previous trial study willing to take part in the follow-up study

Exclusion criteria of follow-up study:

• History of type 1 diabetes

• Taking the cholesterol-lowering drug, an anti-diabetic drug, or oral corticosteroid for more than 2 consecutive weeks in the last 3 months

• Pregnant

Related Conditions & MeSH terms

• Behavior
• Cognitive Function 1, Social
• Depression
• Dyslipidemias
• Insulin Resistance
• Obesity
• Permeability; Increased
• Stunting

Intervention

Dietary Supplement:
• Low Calcium Milk
50 mg calcium/day
• Regular Calcium Milk
400 mg/day
• Probiotic 1
regular calcium milk + probiotic
• Probiotic 2
regular calcium milk + probiotic

Locations

Country	Name	City	State
Indonesia	Human Nutrition Research Center, Indonesian Medical Education Research Institute; and Department of Nutrition, Faculty of Medicine, Universitas Indonesia	Jakarta Pusat	DKI Jakarta

Sponsors (3)

Lead Sponsor	Collaborator
Indonesia University	SEAMEO Regional Centre for Food and Nutrition, Wageningen University

Country where clinical trial is conducted

Indonesia, 

References & Publications (2)

Agustina R, Bovee-Oudenhoven IM, Lukito W, Fahmida U, van de Rest O, Zimmermann MB, Firmansyah A, Wulanti R, Albers R, van den Heuvel EG, Kok FJ. Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years. J Nutr. 2013 Jul;143(7):1184-93. doi: 10.3945/jn.112.166397. Epub 2013 May 22. — View Citation

Agustina R, Kok FJ, van de Rest O, Fahmida U, Firmansyah A, Lukito W, Feskens EJ, van den Heuvel EG, Albers R, Bovee-Oudenhoven IM. Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections in Indonesian children. Pediatrics. 2012 May;129(5):e1155-64. doi: 10.1542/peds.2011-1379. Epub 2012 Apr 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Child's linear growth the age of 11-17 years	Height-for-age z-score based on the WHO Child Growth Standards.	January - March 2019
Primary	Child's height at the age of 11-17 years	Height in meters.	January - March 2019
Primary	Child's weight at the age of 11-17 years	Weight in kilograms.	January - March 2019
Primary	Child's nutritional status at the age of 11-17 years	BMI-for-age z-score based on the WHO Child Growth Standards. BMI was calculated from height and weight measurement.	January - March 2019
Secondary	Gut integrity at the age of 11-17 years	Lactulose-mannitol ratio was calculated by dividing percent excretion of lactulose with percent excretion of mannitol.	January - March 2019
Secondary	Cognitive function assessed using Raven's Progressive Matrices at the age of 11-17 years	Raven's Progressive Matrices (RPM) was administered by psychologists. Raw score of RPM was used to evaluate adolescents' cognition.	January - March 2019
Secondary	Symptoms related to depression assessed using Children Depression Inventory at the age of 11-17 years	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.	January - March 2019
Secondary	Behaviour assessed using Strength and Difficulties Questionnaire at the age of 11-17 years	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.	January - March 2019
Secondary	Serum BDNF at the age of 11-17 years	Serum BDNF in pg/ml was quantified using ELISA method	January - March 2019
Secondary	Triglyceride level at the age of 11-17 years	Triglyceride level in milligrams per decilitre.	January - March 2019
Secondary	High-density lipoprotein level at the age of 11-17 years	High-density lipoprotein level in milligrams per decilitre.	January - March 2019
Secondary	Low-density lipoprotein level at the age of 11-17 years	Low-density lipoprotein level in milligrams per decilitre.	January - March 2019
Secondary	Fasting insulin level at the age of 11-17 years	Fasting insulin level in µU per millilitre	January - March 2019
Secondary	Fasting glucose level at the age of 11-17 years	Fasting glucose level in milligrams per decilitre.	January - March 2019
Secondary	HOMA-IR at the age of 11-17 years	HOMA-IR was quantified by multiplying fasting insulin level with fasting glucose level.	January - March 2019