Nutritional StuntingNCT03895151
Association Between Intakes of Protein, Calcium and Milk With Gene Expression and Linear Growth of School Aged Children
A study testing Milk supplementation and Food Based Recommendation (FBR) nutrition education in people with Nutritional Stunting and Nutritional Anemia, run by SEAMEO Regional Centre for Food and Nutrition at 1 site in Indonesia.
Trial summary
Protein is one type of nutrients known as the cause of stunting in developing countries since the mid-1970s (1) but then less attention on protein intake with the assumption that protein intake is sufficient. Read more about this study
- Who is it for?
- Ages 8 to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Nutritional Stunting, Nutritional Anemia, Nutritional Deficiency
- What is being tested?
- Milk supplementation and Food Based Recommendation (FBR) nutrition education
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteIndonesia
- Study dates
- 24 Jan 2018to 30 Jun 2019
- Phase
- Interventional
- 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 8 to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Primary school children
- Willing to take part in the research and taken venous blood sampling as evidence by the signing of an informed consent from the parents
- Does not suffer from disability
- No complaint such as diarrhea, vomiting or nausea after drinking milk (based on the information of parents during screening)
Who cannot join
- The child not present when taking blood
- Having a history of bleeding such as hemophilia
- Children have plans to move schools within the next 6 months from the baseline data collection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Association Between Intakes of Protein, Calcium, and Milk With Gene Expression and Linear Growth of School Aged Children in Malang
Protein is one type of nutrients known as the cause of stunting in developing countries since the mid-1970s (1) but then less attention on protein intake with the assumption that protein intake is sufficient. Compilation of published and non-published dietary intake research among Indonesian children aged 3-12 years (2), 0-18 years old (3) and 1-3 years old (3) found that protein intake among Indonesian children was sufficient (4). This finding is also confirmed by some other studies in 6 low-income countries and lead to the conclusion that growth restriction is not due to protein deficiency (5). Since then, micronutrient received main attention for the past 4 decades (1) to improve the health and survival of young children in developing countries. Issues on the need to re-examined protein recently emerge after the paper of Semba (1,6) regarding the low circulating amino acid among stunted children. It was hypothesized that the correlation between the low level of circulating amino acid with linear growth was through the mechanism of rapamycin complex C1 (mTORC1) and general control nonderepressible 2 (GCN2) pathway that contributes in the synthesis of sphingolipids and glycerophospholipids (6). However, the mechanism on how amino acid link to linear growth remains unclear.
Fortification among Asian children revealed that only milk as food vehicles reported a significant effect on linear growth (2). It is likely that the effect on linear growth is influenced not only on micronutrient content of the fortified foods but also on protein and amino acid profiles of milk as the food vehicle.
Read the detailed description
Background:
The understanding of stunting has shifted from attention to protein and micronutrients in 60-80s to amino acids and calcium in the past two decades. Amino acids are suspected to be nutrients that determine to stunting because recent studies have shown that growth can be carried out by the information pathway through the mTOR pathway (the mechanistic target of rapamycin). mTOR is a serine/threonine protein kinase from the PI3K family related kinases which are the main subunits of 2 complex proteins, namely mTORC1 and mTORC2. The mTORC1 protein includes 5 main parts for cell growth, nutrition, growth factors, oxygen, energy, and stress. The mTORC2 protein is used in the cytoskeletal organization and cell survival. The activated mTORC1 protein initiates anabolic processes such as synthetic proteins, lipids, and nucleotides and inhibits catabolic processes such as autophagy. mTORC1 consists of three core proteins: mTOR, Raptor (regulatory protein associated with mTOR) and mLST8 (deadly mammals with Sec13 protein 8).
Activation of the mTORC1 pathway as a controller of growth and metabolism is in accordance with the adequacy of intracellular essential amino acids. Deficiency of leucine, isoleucine, and valine determines mTOR downregulation. Inadequate intake of essential amino acids will repress protein and lipid synthesis as well as cell growth that will affect bone and chondral palate growth, skeletal muscle growth, nervous system myelinization, immune function and the size of the organ formed (Saxton \& Sabatini, 2017). Research by Semba, et.al (2016) shows that in stunting children's serum, the levels of the nine essential amino acids are very low. Given that the body does not form essential amino acids directly, the intake of amino acids from food becomes very important (Nuss \& Tanumihardjo, 2011). Essential amino acids are mostly contained in animal protein, but consumption in developing countries is still limited. Consumption of animal food sources is associated with a lower risk of stunting.
Study of the mTORC1 pathway that has been done in vitro studies and experimental animals. In humans, the evidence of amino acid signaling through the mTORC1 pathway by using metabolomic aspects and proteomic and transcriptomic characteristics is still unknown. Analysis of genes related to MTORC1 pathway may answer this question
The scope of services:
- To assess intakes of energy, macronutrients (protein, fat, carbohydrate), calcium and other micronutrients related to growth (zinc, iron, magnesium)
- To assess linear growth
- To assess gene expression of the mTORC1 pathway in school-age children in Malang, East Java.
The objective of research:
- To assess energy and nutrient intake (especially for protein and calcium)
- To assess the expression of mTOR gene
- To assess the linear growth (height)
- To assess the association between intake of protein, calcium, milk with gene expression of mTOR and linear growth of children who received food-based intervention with or without milk with comparable calcium and protein intakes
- Conditions
- Nutritional Stunting, Nutritional Anemia, Nutritional Deficiency, Nutrigenetic, Nutrigenomic, Linear Programming
- Being tested
- Milk supplementation, Food Based Recommendation (FBR) nutrition education
- Medical subject headings
- Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milk supplementationDietary supplement
Fresh milk from local farmer. No artificial sweetener and preservatives. Brandless.
Food Based Recommendation (FBR) nutrition educationOther
Food Based Recommendation is result of OPTIFOOD WHO that analysed local food to optimize nutritional status according to problem nutrient.
| Study group | Role | What they receive |
|---|---|---|
| Milk supplementation | Experimental | Children will receive 130 ml fresh milk, 6 days/week for 20 weeks (January-June 2019).
Milk will be provided and delivered by appointed supplier directly to school. Milk will be distributed with name of the student on the bottle - during break time.
Subjects must be consumed with supervision of the teacher at school during the break.
If they can not finish the milk at once, they can store it in the provided cool box. Student then can consume it again before they go home. Teacher have to record the remaining milk in each bottle that corresponds to every child name and record it in the provided form.
Prior to holiday, student will be given the milk according to school leave days.
Enumerators should collect the form every 3 days and make a recap in the provided form. Receives: Dietary Supplement: Milk supplementation |
| Food Based Recommendation (FBR) nutrition education | Experimental | FBR group will received nutrition education delivered by trained teacher under the supervision of researcher/research assistant once a week. Those who received nutrition education is not only the recruited subjects but also includes their classmates. Receives: Other: Food Based Recommendation (FBR) nutrition education |
| Control | No intervention | Control group will receive standard nutrition education |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increasing of children height who receive intervention from baseline
Height of the subject will be measured using Shorrboard. Height measurement will be taken twice, the difference between 1st and 2nd measurements should be not more than 0.7 cm. The data analyzed using WHO AnthroPlus to obtain height for age z-score (HAZ) of the subject.
Measured: 3 days in end-line of study
Secondary outcomes (3)
nutrient intakes
Dietary of energy intake, macronutrients, calcium and other micronutrients related to growth will be assessed using 24-hour recall with multiple-pass interviewing technique. The analysis will be performed using Nutrisurvey 2017 with Indonesian food composition table.
Measured: 3 days in baseline and end-line
VDR Gene Polymorphism of SNP rs4516035 and rs11568820
The SNP Genotyping assay analyzed using Real Time PCR and StepOne V2.3 Software. A total of 40 cycles will performed. The cycling steps of the analysis are Hold (95oC, 20s), Denaturation (95oC, 3s), Annealing Extension (60oC, 20s). The total running time was about one and a half hours for 40 cycles.
Measured: in middle of study (2 months after baseline)
gene expression of mTORC1 pathway
The expression of 5' TOP genes as biomarker of downstream mTORC1 pathway will be analyzed using RT-qPCR and StepOne V2.3 Software. mRNA quantified by SYBR Green reaction. A total of 40 cycles will performed. The cycling steps of the analysis are UDG activation (50oC, 2min), Dual-Lock DNA polymerase (95oC, 2min), Denaturation (95oC, 3s), Annealing Extension (60oC, 30s). The total running time was about half an hour for 40 cycles.
Measured: 3 days in end-line of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2019
- Study start24 Jan 2018
- Primary completion15 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nutritional StuntingStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- SEAMEO Regional Centre for Food and Nutrition
- Sponsor type
- University, hospital or other
- Collaborators
- Direktorat Riset dan Pengabdian Masyarakat Universitas Indonesia, University of Brawijaya
- Responsible party
- Principal investigator, Dr.Umi Fahmida, SEAMEO Regional Centre for Food and Nutrition
- Investigators
- Umi Fahmida Fahmida, Dr, Principal investigator, SEAMEO RECFON
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03895151
- Sponsor's protocol ID
- NGMilkMalang
- Status last verified
- Dec 2019
- First submitted
- 20 Jan 2019
- Last updated
- 3 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Intakes of Protein, Calcium, and Milk With Gene Expression and Linear Growth of School Aged Children in Malang
- ClinicalTrials.gov ID
- NCT03895151
- Acronym / sponsor ID
- NGMilkMalang
- Conditions
- Nutritional Stunting, Nutritional Anemia, Nutritional Deficiency, Nutrigenetic, Nutrigenomic, Linear Programming
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- SEAMEO Regional Centre for Food and NutritionUniversity, hospital or other
- Collaborators
- Direktorat Riset dan Pengabdian Masyarakat Universitas Indonesia, University of Brawijaya
- Study start
- 24 Jan 2018 (actual)
- Primary completion
- 15 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 29 Mar 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.
Protein is one type of nutrients known as the cause of stunting in developing countries since the mid-1970s (1) but then less attention on protein intake with the assumption that protein intake is sufficient. Compilation of published and non-published dietary intake research among Indonesian children aged 3-12 years (2), 0-18 years old (3) and 1-3 years old (3) found that protein intake among Indonesian children was sufficient (4). This finding is also confirmed by some other studies in 6 low-income countries and lead to the conclusion that growth restriction is not due to protein deficiency (5). Since then, micronutrient received main attention for the past 4 decades (1) to improve the health and survival of young children in developing countries. Issues on the need to re-examined protein recently emerge after the paper of Semba (1,6) regarding the low circulating amino acid among stunted children. It was hypothesized that the correlation between the low level of circulating amino acid with linear growth was through the mechanism of rapamycin complex C1 (mTORC1) and general control nonderepressible 2 (GCN2) pathway that contributes in the synthesis of sphingolipids and glycerophospholipids (6). However, the mechanism on how amino acid link to linear growth remains unclear.
Fortification among Asian children revealed that only milk as food vehicles reported a significant effect on linear growth (2). It is likely that the effect on linear growth is influenced not only on micronutrient content of the fortified foods but also on protein and amino acid profiles of milk as the food vehicle.
Detailed description
Background:
The understanding of stunting has shifted from attention to protein and micronutrients in 60-80s to amino acids and calcium in the past two decades. Amino acids are suspected to be nutrients that determine to stunting because recent studies have shown that growth can be carried out by the information pathway through the mTOR pathway (the mechanistic target of rapamycin). mTOR is a serine/threonine protein kinase from the PI3K family related kinases which are the main subunits of 2 complex proteins, namely mTORC1 and mTORC2. The mTORC1 protein includes 5 main parts for cell growth, nutrition, growth factors, oxygen, energy, and stress. The mTORC2 protein is used in the cytoskeletal organization and cell survival. The activated mTORC1 protein initiates anabolic processes such as synthetic proteins, lipids, and nucleotides and inhibits catabolic processes such as autophagy. mTORC1 consists of three core proteins: mTOR, Raptor (regulatory protein associated with mTOR) and mLST8 (deadly mammals with Sec13 protein 8).
Activation of the mTORC1 pathway as a controller of growth and metabolism is in accordance with the adequacy of intracellular essential amino acids. Deficiency of leucine, isoleucine, and valine determines mTOR downregulation. Inadequate intake of essential amino acids will repress protein and lipid synthesis as well as cell growth that will affect bone and chondral palate growth, skeletal muscle growth, nervous system myelinization, immune function and the size of the organ formed (Saxton \& Sabatini, 2017). Research by Semba, et.al (2016) shows that in stunting children's serum, the levels of the nine essential amino acids are very low. Given that the body does not form essential amino acids directly, the intake of amino acids from food becomes very important (Nuss \& Tanumihardjo, 2011). Essential amino acids are mostly contained in animal protein, but consumption in developing countries is still limited. Consumption of animal food sources is associated with a lower risk of stunting.
Study of the mTORC1 pathway that has been done in vitro studies and experimental animals. In humans, the evidence of amino acid signaling through the mTORC1 pathway by using metabolomic aspects and proteomic and transcriptomic characteristics is still unknown. Analysis of genes related to MTORC1 pathway may answer this question
The scope of services:
- To assess intakes of energy, macronutrients (protein, fat, carbohydrate), calcium and other micronutrients related to growth (zinc, iron, magnesium)
- To assess linear growth
- To assess gene expression of the mTORC1 pathway in school-age children in Malang, East Java.
The objective of research:
- To assess energy and nutrient intake (especially for protein and calcium)
- To assess the expression of mTOR gene
- To assess the linear growth (height)
- To assess the association between intake of protein, calcium, milk with gene expression of mTOR and linear growth of children who received food-based intervention with or without milk with comparable calcium and protein intakes
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Milk supplementation | Experimental | Dietary Supplement: Milk supplementationChildren will receive 130 ml fresh milk, 6 days/week for 20 weeks (January-June 2019). Milk will be provided and delivered by appointed supplier directly to school. Milk will be distributed with name of the student on the bottle - during break time. Subjects must be consumed with supervision of the teacher at school during the break. If they can not finish the milk at once, they can store it in the provided cool box. Student then can consume it again before they go home. Teacher have to record the remaining milk in each bottle that corresponds to every child name and record it in the provided form. Prior to holiday, student will be given the milk according to school leave days. Enumerators should collect the form every 3 days and make a recap in the provided form. |
| Food Based Recommendation (FBR) nutrition education | Experimental | Other: Food Based Recommendation (FBR) nutrition educationFBR group will received nutrition education delivered by trained teacher under the supervision of researcher/research assistant once a week. Those who received nutrition education is not only the recruited subjects but also includes their classmates. |
| Control | No intervention | –Control group will receive standard nutrition education |
Who may qualify
- Ages
- 8 to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Primary school children
- Willing to take part in the research and taken venous blood sampling as evidence by the signing of an informed consent from the parents
- Does not suffer from disability
- No complaint such as diarrhea, vomiting or nausea after drinking milk (based on the information of parents during screening)
Key exclusion criteria (3 listed)
- The child not present when taking blood
- Having a history of bleeding such as hemophilia
- Children have plans to move schools within the next 6 months from the baseline data collection.
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 |
|---|---|---|
| Milk supplementationFresh milk from local farmer. No artificial sweetener and preservatives. Brandless. | Dietary supplement | Milk supplementation |
| Food Based Recommendation (FBR) nutrition educationFood Based Recommendation is result of OPTIFOOD WHO that analysed local food to optimize nutritional status according to problem nutrient. | Other | Food Based Recommendation (FBR) nutrition education |
Primary outcome
Increasing of children height who receive intervention from baseline
Time frame: 3 days in end-line of study
Height of the subject will be measured using Shorrboard. Height measurement will be taken twice, the difference between 1st and 2nd measurements should be not more than 0.7 cm. The data analyzed using WHO AnthroPlus to obtain height for age z-score (HAZ) of the subject.
3 secondary outcomes
nutrient intakes
Time frame: 3 days in baseline and end-line
VDR Gene Polymorphism of SNP rs4516035 and rs11568820
Time frame: in middle of study (2 months after baseline)
gene expression of mTORC1 pathway
Time frame: 3 days in end-line of study
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 3 Dec 2019.
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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.
Umi Fahmida Fahmida, Dr principal investigator
SEAMEO RECFON
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Milk supplementation and Food Based Recommendation (FBR) nutrition education in people with Nutritional Stunting and Nutritional Anemia, run by SEAMEO Regional Centre for Food and Nutrition 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 3 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 3 Dec 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?
Increasing of children height who receive intervention from baseline (time frame: 3 days in end-line of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Dec 2019.