Health BehaviorDIVINENCT05623007
Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection
A study testing Probiotics and Counselling on healthy eating, physical activity, and psychosocial stimulation in people with Health Behavior and Child Development, run by Universitas Indonesia at 1 site in Indonesia.
Trial summary
Probiotic intervention has been currently suggested to provide supportive benefits in promoting health, including alleviating disease symptoms, protecting against diarrhea and respiratory infection, affecting growth and modulating the immune system by improving the beneficial gut microbiota colonization, giving… Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Health Behavior, Child Development, Adolescent Obesity
- What is being tested?
- Probiotics and Counselling on healthy eating, physical activity, and psychosocial stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 440 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Nov 2022to 30 Dec 2025
- Phase
- Interventional
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 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- living in Jakarta, Surabaya, and Yogyakarta City for at least 6 months permanently;
- apparently healthy;
- male and female, age 12-17 years old;
- overweight or obese (BMI-for-age z-score >+1SD);
- have completed at least two dosages of COVID-19 vaccine, the vaccine must be CoronaVac® (Sinovac);
- minimal 6 months post vaccinated prior to recruitments.
- parents willing to sign the informed consent and adolescents give informed assent;
- Must have an active health insurance, for instance BPJS or similar health insurance.
Who cannot join
- having a history of COVID-19 infection within the last month confirmed by PCR or antigen from health care facilities or independent laboratory;
- having a history of chronic and non-communicable diseases, congenital diseases, and disabilities;
- reported current diagnosed as suspected active Tuberculosis (primary lung TB, miliary TB, bleeding cough bone TB, meningitis TB);
- having a history of gastrointestinal or malabsorption disorder (such as celiac disease and inflammatory bowel disease) within the last three months or during the study;
- taking antibiotics during 2 weeks before the start of the study (adolescents will be included after 3 weeks of last antibiotic intake);
- taking other medications or having diseases that may influence the immune response - i.e. immune deficiencies, immunosuppressants medications, blood transfusion or other blood products;
- taking insulin and/or anti-dyslipidemia medication;
- being pregnant and/or breastfeeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Indonesia1 site, 1 recruiting
- Recruiting
Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
Jakarta Pusat, DKI Jakarta, 10430
Rina Agustina, PhD, +6221 2912477, dr.rinaagustina@gmail.com
Rina Agustina, PhD
About this study
Official title: Dietary Modulation of Gut Microbiota on Nutritional Status and COVID-19 Infection in Adolescents: Gut-Lung-Axis
Probiotic intervention has been currently suggested to provide supportive benefits in promoting health, including alleviating disease symptoms, protecting against diarrhea and respiratory infection, affecting growth and modulating the immune system by improving the beneficial gut microbiota colonization, giving direction on the gut-lung-axis pathway. This indicates that probiotics may become alternative to improve nutrition and reduce the risk of viral infections which may reduce the risk against Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). Introduction to probiotics during adolescence can alleviate inflammation and invert dysbiosis. However, evidence on the effect of probiotic supplementation on enhancing antibody response to SARS COV-2 in adolescents is lacking. Moreover, previous studies showed the potential effect of probiotic supplementation to improve overweight and obesity in adolescents. A bi-directional relationship exists among nutrition, infection, and immunity as changes in one element will affect the others. The main objective of this study is to investigate the effect of dietary modulation of overweight and obese adolescent's gut microbiota through probiotic supplementation combined with healthy eating and physical activity counseling and psychosocial stimulation on nutritional status and antibody response to COVID-19 vaccination. This trial will conduct a 20-week intervention for overweight and obese adolescents.
Read the detailed description
The adolescence period is the transition from childhood to adulthood. Adolescents are vulnerable to many biomedical exposures, such as a low-quality diet, fewer fruits and vegetable intake, low physical activities, smoking habits, and alcohol consumption; and non-biomedical aspects such as mental depression, parental distress, and household income, which were known to be associated with increased risk of many health outcomes. Obese adolescents are vulnerable to many infections, poor disease outcomes and complications, and lower antibody response to vaccinations. Studies that have investigated Covid-19 incidence in overweight and obese individuals are still scarce. Adolescence is also a sensitive period to microbial change or dysbiosis due to practicing poor diet, low physical activity, inadequate sleep, stress, and substance use (smoking, drugs, and alcohol). Despite the existing prevalence of SARS-COV-2 infections is increasing in adolescents, and the vaccine program is not prioritized in this population, making the prevention strategy for SARS-COV-2 infection may become less effective in this population. Besides, low-quality diet and lifestyle habits and family cluster transmission at home are often not fully addressed in the policy. These factors may be the contributors to the potential highest COVID-19 exposure for children and adolescents. Since exposure among adolescents is linked to serious adverse health effects, effective interventions to improve nutritional outcomes and reduce the risk of COVID-19 infection will provide substantial long-term returns. However, such interventions for adolescents in Indonesia and globally are lacking.
This study is a randomized clinical trial (RCT) and placebo parallel controlled study. The research will be conducted in junior and senior high schools in Jakarta, Surabaya, and Yogyakarta, Indonesia.
In light of COVID-19 outbreak, if face-to-face activities are permitted by (1) national government (Indonesian Ministry of Health), (2) local government (DKI Jakarta), (3) the university, (4) Data Safety Monitoring Board, and (5) by consent of the subject, then the activities need to be strictly adjusted with the COVID-19 prevention measures for both personnel and subjects. All personnel and subjects who will be involved in the activities are required to fill out the COVID-19 symptom screening form prior to the visit and have been vaccinated with a complete dose.
- Conditions
- Health Behavior, Child Development, Adolescent Obesity
- Being tested
- Probiotics, Counselling on healthy eating, physical activity, and psychosocial stimulation, Placebo probiotics
- Keywords
- adolescent, probiotics, COVID-19, overweight, obese
- Medical subject headings
- Health Behavior, Pediatric Obesity, COVID-19, Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticsDietary supplement
Combination of 3 probiotic strains: Lactobacillus rhamnosus (LGG), Bifidobacterium animalis subsp. lactis (BB-12), and Lactobacillus acidophilus (LA-5)
Counselling on healthy eating, physical activity, and psychosocial stimulationBehavioural
Counselling on healthy eating, physical activity, and psychosocial stimulation.
Placebo probioticsDietary supplement
Maltodextrin
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | 220 overweight/obese adolescents will be given Probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation. Receives: Dietary Supplement: Probiotics; Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation |
| Control | Placebo comparator | 220 overweight/obese adolescents will be given placebo probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation. Receives: Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation; Dietary Supplement: Placebo probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
BMI-for-age z-scores (BAZ)
Change in BAZ obtain from anthropometric measurements, i.e., weight (kg) and height (m) converted to BMI
Measured: 5, 10, 15, and 20 weeks
Immunoglobulin G (IgG) specific to SARS-COV-2 titer concentrations
Change in IgG specific to SARS-COV-2 titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)
Measured: 10 and 20 weeks
Secondary outcomes (5)
α-gut microbiota diversity
Change in α-diversity measured by 1) Chao1, 2) phylogenetic diversity, and 3) the Shannon index.
Measured: 20 weeks
β-gut microbiota diversity
Change in β -diversity: as the variability in community composition (the identity of taxa observed) among samples
Measured: 20 weeks
Monoclonal antibody affinity against SARS-COV-2
Change in equilibrium dissociation constant (KD) of monoclonal antibody against SARS-COV-2 spike protein measured by competitive ELISA
Measured: 10 and 20 weeks
Secretory Immunoglobulin A (sIgA) specific to SARS-COV-2 titer concentrations
Change in sIgA specific to SARS-COV-2 titer concentrations assessed by competitive ELISA
Measured: 10 and 20 weeks
Dietary quality
Change in score of dietary quality assessed by Healthy Eating Index 2015 from 24 hour recalls data
Measured: 5, 10, 15, and 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2022
- Study start1 Nov 2022
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Health BehaviorStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The product will be given to 440 overweight/obese adolescents, 220 adolescents as an intervention group, and 220 overweight/obese adolescents as a control group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Collaborators
- Gadjah Mada University, Universitas Airlangga, University of Melbourne, The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
- Responsible party
- Principal investigator, Prof Rina Agustina, MD, PhD, Universitas Indonesia
- Investigators
- Rina Agustina, PhD, Principal investigator, Dep of Nutrition and Human Nutrition Research Center, IMERI, Fac of Medicine Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05623007
- Sponsor's protocol ID
- DIVINE
- Acronym
- DIVINE
- Status last verified
- Feb 2025
- First submitted
- 31 Oct 2022
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will make data from the clinical trials available upon reasonable request subject to approval from the Ministry of Health of the Republic of Indonesia. This will be in accordance with the following regulations: (1) Regulation of the Ministry of Health No. 85 Year 2020 concerning the Transfer and Use of Materials, Information Content, and Data; (2) Law No. 17 Year 2023 on Health; (3) Government Regulation No. 28 Year 2024 on the Implementation Regulation of Law No. 17 of 2023 on Health; (4) Law No. 27 of 2022 on Personal Data Protection. The individual data will be kept anonymous.
Publications
Petta I, Fraussen J, Somers V, Kleinewietfeld M. Interrelation of Diet, Gut Microbiome, and Autoantibody Production. Front Immunol. 2018 Mar 6;9:439. doi: 10.3389/fimmu.2018.00439. eCollection 2018.
PubMed 29559977Rajput S, Paliwal D, Naithani M, Kothari A, Meena K, Rana S. COVID-19 and Gut Microbiota: A Potential Connection. Indian J Clin Biochem. 2021 Jul;36(3):266-277. doi: 10.1007/s12291-020-00948-9. Epub 2021 Jan 21.
PubMed 33495676Agustina 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 22492764Abenavoli L, Scarpellini E, Colica C, Boccuto L, Salehi B, Sharifi-Rad J, Aiello V, Romano B, De Lorenzo A, Izzo AA, Capasso R. Gut Microbiota and Obesity: A Role for Probiotics. Nutrients. 2019 Nov 7;11(11):2690. doi: 10.3390/nu11112690.
PubMed 31703257Agustina R, Ekawidyani KR, Mutiyani M, Prafiantini E, Nindya TS, Damayanti W, Rejeki PS, Djuari L, Huriyati E, Bines JE, Juffrie M. Study protocol for a randomised controlled trial evaluating the efficacy of dietary modulation of probiotics on nutritional status and antibody response to SARS-CoV-2 in Indonesian adolescents: gut-lung axis (DIVINE). BMJ Open. 2025 Apr 2;15(4):e087934. doi: 10.1136/bmjopen-2024-087934.
PubMed 40180370