Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection

NCT ID: NCT05623007

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-12-30

Brief 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 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention

220 overweight/obese adolescents will be given Probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.

Group Type: EXPERIMENTAL

Probiotics

Intervention Type: DIETARY_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 stimulation

Intervention Type: BEHAVIORAL

Counselling on healthy eating, physical activity, and psychosocial stimulation.

Control

220 overweight/obese adolescents will be given placebo probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.

Group Type: PLACEBO_COMPARATOR

Counselling on healthy eating, physical activity, and psychosocial stimulation

Intervention Type: BEHAVIORAL

Counselling on healthy eating, physical activity, and psychosocial stimulation.

Placebo probiotics

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Interventions

Probiotics

Combination of 3 probiotic strains: Lactobacillus rhamnosus (LGG), Bifidobacterium animalis subsp. lactis (BB-12), and Lactobacillus acidophilus (LA-5)

Intervention Type: DIETARY_SUPPLEMENT

Counselling on healthy eating, physical activity, and psychosocial stimulation

Counselling on healthy eating, physical activity, and psychosocial stimulation.

Intervention Type: BEHAVIORAL

Placebo probiotics

Maltodextrin

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. living in Jakarta, Surabaya, and Yogyakarta City for at least 6 months permanently;

2. apparently healthy;

3. male and female, age 12-17 years old;

4. overweight or obese (BMI-for-age z-score >+1SD);

5. have completed at least two dosages of COVID-19 vaccine, the vaccine must be CoronaVac® (Sinovac);

6. minimal 6 months post vaccinated prior to recruitments.

7. parents willing to sign the informed consent and adolescents give informed assent;

8. Must have an active health insurance, for instance BPJS or similar health insurance.

Exclusion Criteria

1. having a history of COVID-19 infection within the last month confirmed by PCR or antigen from health care facilities or independent laboratory;

2. having a history of chronic and non-communicable diseases, congenital diseases, and disabilities;

3. reported current diagnosed as suspected active Tuberculosis (primary lung TB, miliary TB, bleeding cough bone TB, meningitis TB);

4. 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;

5. taking antibiotics during 2 weeks before the start of the study (adolescents will be included after 3 weeks of last antibiotic intake);

6. taking other medications or having diseases that may influence the immune response - i.e. immune deficiencies, immunosuppressants medications, blood transfusion or other blood products;

7. taking insulin and/or anti-dyslipidemia medication;

8. being pregnant and/or breastfeeding.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gadjah Mada University

OTHER

Sponsor Role: collaborator

Universitas Airlangga

OTHER

Sponsor Role: collaborator

University of Melbourne

OTHER

Sponsor Role: collaborator

The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia

UNKNOWN

Sponsor Role: collaborator

Indonesia University

OTHER

Sponsor Role: lead

Responsible Party

Prof Rina Agustina, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rina Agustina, PhD

Role: PRINCIPAL_INVESTIGATOR

Dep of Nutrition and Human Nutrition Research Center, IMERI, Fac of Medicine Universitas Indonesia

Locations

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, Indonesia

Site Status: RECRUITING

Countries

Indonesia

Central Contacts

Rina Agustina, PhD

Role: CONTACT

dr.rinaagustina@gmail.com

+622129189160 ext. 201052

Rahyussalim Rahyussalim, PhD

Role: CONTACT

manajer.riset.fkui1@gmail.com

+622129189160 ext. 201908

Facility Contacts

Rina Agustina, PhD

Role: primary

dr.rinaagustina@gmail.com

+6221 2912477

References

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.

Reference Type: BACKGROUND

PMID: 29559977 (View on PubMed)

Rajput 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.

Reference Type: BACKGROUND

PMID: 33495676 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22492764 (View on PubMed)

Abenavoli 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.

Reference Type: BACKGROUND

PMID: 31703257 (View on PubMed)

Agustina 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.

Reference Type: DERIVED

PMID: 40180370 (View on PubMed)

Other Identifiers

DIVINE

Identifier Type: -

Identifier Source: org_study_id