StuntingPROBIOCALNCT04046289
Effects of Probiotics and Calcium Supplementation on Growth, Development, and Metabolic Parameters
An observational study of Stunting and Obesity, run by Universitas Indonesia at 1 site in Indonesia.
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. Read more about this study
- Who is it for?
- Ages 11 to 17 years
- Conditions the study is for
- Stunting, Obesity, Cognitive Function 1, Social
- What is being tested?
- Low Calcium Milk, Regular Calcium Milk and Probiotic 1
- How many people
- 238 participants
- Where
- 1 siteIndonesia
- Study dates
- 26 Jan 2019to 5 Jul 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Low-socioeconomic urban communities representing flooding and non-flooding areas of East Jakarta, Indonesia.
Who may be able to join
- 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)
- Healthy adolescent participated in the previous trial study willing to take part in the follow-up study
Who cannot join
- 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
Show all 11Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
Human Nutrition Research Center, Indonesian Medical Education Research Institute; and Department of Nutrition, Faculty of Medicine, Universitas Indonesia
Jakarta Pusat, DKI Jakarta, 13420
About this study
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
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.
Read the 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.
- Conditions
- Stunting, Obesity, Cognitive Function 1, Social, Depression, Behavior, Dyslipidemias
- Being tested
- Low Calcium Milk, Regular Calcium Milk, Probiotic 1, Probiotic 2
- Medical subject headings
- Growth Disorders, Obesity, Depression, Behavior, Dyslipidemias, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Calcium MilkDietary supplement
50 mg calcium/day
Regular Calcium MilkDietary supplement
400 mg/day
Probiotic 1Dietary supplement
regular calcium milk + probiotic
Probiotic 2Dietary supplement
regular calcium milk + probiotic
| Study group | Role | What they receive |
|---|---|---|
| Low Calcium | low calcium milk of 180 ml, twice daily for 24 weeks Receives: Dietary Supplement: Low Calcium Milk | |
| Regular Calcium | regular calcium milk of 180 ml, twice daily for 24 weeks Receives: Dietary Supplement: Regular Calcium Milk | |
| Probiotic 1 | regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks Receives: Dietary Supplement: Probiotic 1 | |
| Probiotic 2 | regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks Receives: Dietary Supplement: Probiotic 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Child's linear growth the age of 11-17 years
Height-for-age z-score based on the WHO Child Growth Standards.
Measured: January - March 2019
Child's height at the age of 11-17 years
Height in meters.
Measured: January - March 2019
Child's weight at the age of 11-17 years
Weight in kilograms.
Measured: January - March 2019
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.
Measured: January - March 2019
Secondary outcomes (11)
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.
Measured: January - March 2019
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.
Measured: January - March 2019
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.
Measured: January - March 2019
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.
Measured: January - March 2019
Serum BDNF at the age of 11-17 years
Serum BDNF in pg/ml was quantified using ELISA method
Measured: January - March 2019
Triglyceride level at the age of 11-17 years
Triglyceride level in milligrams per decilitre.
Measured: January - March 2019
High-density lipoprotein level at the age of 11-17 years
High-density lipoprotein level in milligrams per decilitre.
Measured: January - March 2019
Low-density lipoprotein level at the age of 11-17 years
Low-density lipoprotein level in milligrams per decilitre.
Measured: January - March 2019
Fasting insulin level at the age of 11-17 years
Fasting insulin level in μU per millilitre
Measured: January - March 2019
Fasting glucose level at the age of 11-17 years
Fasting glucose level in milligrams per decilitre.
Measured: January - March 2019
HOMA-IR at the age of 11-17 years
HOMA-IR was quantified by multiplying fasting insulin level with fasting glucose level.
Measured: January - March 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2019
- Study start26 Jan 2019
- Primary completion3 Mar 2019
- Study completion5 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for StuntingStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 238 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Collaborators
- SEAMEO Regional Centre for Food and Nutrition, Wageningen University
- Responsible party
- Principal investigator, Rina Agustina, Universitas Indonesia
- Investigators
- Rina Agustina, PhD, Principal investigator, HNRC IMERI; Department of Nutrition, Faculty of Medicine, Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04046289
- Sponsor's protocol ID
- probiocal
- Acronym
- PROBIOCAL
- Status last verified
- Aug 2019
- First submitted
- 1 Aug 2019
- Last updated
- 7 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22492764Agustina 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.
PubMed 23700339Agustina R, Rianda D, Setiawan EA. Relationships of Child-, Parents-, and Environment-Associated Determinants with Diet Quality, Physical Activity, and Smoking Habits Among Indonesian Urban Adolescents. Food Nutr Bull. 2022 Mar;43(1):44-55. doi: 10.1177/03795721211046145. Epub 2021 Oct 21.
PubMed 34670443Setiawan EA, Rianda D, Kadim M, Meilianawati, Susanto F, Kok FJ, Shankar AH, Agustina R. Tenth year reenrollment randomized trial investigating the effects of childhood probiotics and calcium supplementation on height and weight at adolescence. Sci Rep. 2021 Jun 4;11(1):11860. doi: 10.1038/s41598-021-88819-y.
PubMed 34088920
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04046289
- Acronym / sponsor ID
- PROBIOCAL / probiocal
- Conditions
- Stunting, Obesity, Cognitive Function 1, Social, Depression, Behavior, Dyslipidemias
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 238 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Collaborators
- SEAMEO Regional Centre for Food and Nutrition, Wageningen University
- Study start
- 26 Jan 2019 (actual)
- Primary completion
- 3 Mar 2019 (actual)
- Study completion
- 5 Jul 2019 (actual)
- First posted
- 6 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Calcium | – | Dietary Supplement: Low Calcium Milklow calcium milk of 180 ml, twice daily for 24 weeks |
| Regular Calcium | – | Dietary Supplement: Regular Calcium Milkregular calcium milk of 180 ml, twice daily for 24 weeks |
| Probiotic 1 | – | Dietary Supplement: Probiotic 1regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks |
| Probiotic 2 | – | Dietary Supplement: Probiotic 2regular calcium milk of 180 ml + probiotic, twice daily for 24 weeks |
Who may qualify
- Ages
- 11 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Low-socioeconomic urban communities representing flooding and non-flooding areas of East Jakarta, Indonesia.
Key inclusion criteria (4 listed)
- 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)
- Healthy adolescent participated in the previous trial study willing to take part in the follow-up study
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Calcium Milk50 mg calcium/day | Dietary supplement | Low Calcium |
| Regular Calcium Milk400 mg/day | Dietary supplement | Regular Calcium |
| Probiotic 1regular calcium milk + probiotic | Dietary supplement | Probiotic 1 |
| Probiotic 2regular calcium milk + probiotic | Dietary supplement | Probiotic 2 |
Primary outcome
Child's linear growth the age of 11-17 years
Time frame: 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
Time frame: January - March 2019
Height in meters.
Child's weight at the age of 11-17 years
Time frame: January - March 2019
Weight in kilograms.
Child's nutritional status at the age of 11-17 years
Time frame: January - March 2019
BMI-for-age z-score based on the WHO Child Growth Standards. BMI was calculated from height and weight measurement.
11 secondary outcomes
Gut integrity at the age of 11-17 years
Time frame: January - March 2019
Cognitive function assessed using Raven's Progressive Matrices at the age of 11-17 years
Time frame: January - March 2019
Symptoms related to depression assessed using Children Depression Inventory at the age of 11-17 years
Time frame: January - March 2019
Behaviour assessed using Strength and Difficulties Questionnaire at the age of 11-17 years
Time frame: January - March 2019
Serum BDNF at the age of 11-17 years
Time frame: January - March 2019
Triglyceride level at the age of 11-17 years
Time frame: January - March 2019
High-density lipoprotein level at the age of 11-17 years
Time frame: January - March 2019
Low-density lipoprotein level at the age of 11-17 years
Time frame: January - March 2019
Fasting insulin level at the age of 11-17 years
Time frame: January - March 2019
Fasting glucose level at the age of 11-17 years
Time frame: January - March 2019
HOMA-IR at the age of 11-17 years
Time frame: January - March 2019
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
- Background: PubMed 22492764Agustina 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.
- Background: PubMed 23700339Agustina 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.
- Derived from this study: PubMed 34670443Agustina R, Rianda D, Setiawan EA. Relationships of Child-, Parents-, and Environment-Associated Determinants with Diet Quality, Physical Activity, and Smoking Habits Among Indonesian Urban Adolescents. Food Nutr Bull. 2022 Mar;43(1):44-55. doi: 10.1177/03795721211046145. Epub 2021 Oct 21.
- Derived from this study: PubMed 34088920Setiawan EA, Rianda D, Kadim M, Meilianawati, Susanto F, Kok FJ, Shankar AH, Agustina R. Tenth year reenrollment randomized trial investigating the effects of childhood probiotics and calcium supplementation on height and weight at adolescence. Sci Rep. 2021 Jun 4;11(1):11860. doi: 10.1038/s41598-021-88819-y.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rina Agustina, PhD principal investigator
HNRC IMERI; Department of Nutrition, Faculty of Medicine, Universitas Indonesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stunting and Obesity, run by Universitas Indonesia at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Child's linear growth the age of 11-17 years (time frame: January - March 2019). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04046289, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.