Clinical trial NCT05623007: Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection
Official title: Dietary Modulation of Gut Microbiota on Nutritional Status and COVID-19 Infection in Adolescents: Gut-Lung-Axis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Health Behavior
Child Development
Adolescent Obesity
Keywords: adolescent
probiotics
COVID-19
overweight
obese
Lead sponsor: Indonesia University
Sponsor class: OTHER
Collaborators: name: Gadjah Mada University
name: Universitas Airlangga
name: University of Melbourne
name: The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
First posted: 2022-11-21
Enrollment: 440
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: BMI-for-age z-scores (BAZ)
timeFrame: 5, 10, 15, and 20 weeks
measure: Immunoglobulin G (IgG) specific to SARS-COV-2 titer concentrations
timeFrame: 10 and 20 weeks
Secondary outcomes:
measure: α-gut microbiota diversity
timeFrame: 20 weeks
measure: β-gut microbiota diversity
timeFrame: 20 weeks
measure: Monoclonal antibody affinity against SARS-COV-2
timeFrame: 10 and 20 weeks
measure: Secretory Immunoglobulin A (sIgA) specific to SARS-COV-2 titer concentrations
timeFrame: 10 and 20 weeks
measure: Dietary quality
timeFrame: 5, 10, 15, and 20 weeks
Other outcomes:
measure: SARS-COV-2 infection
timeFrame: 20 weeks
measure: Body height
timeFrame: 5, 10, 15, and 20 weeks
measure: Abdominal obesity (waist circumference)
timeFrame: 5, 10, 15, and 20 weeks
measure: Abdominal obesity (waist-hip ratio)
timeFrame: 5, 10, 15, and 20 weeks
measure: Middle upper arm circumference
timeFrame: 5, 10, 15, and 20 weeks
measure: Immunoglobulin M (IgM) against SARS-Cov-2
timeFrame: 10 and 20 weeks
measure: Neutralizing antibody against SARS-Cov-2
timeFrame: 10 and 20 weeks
measure: Gut integrity (zonulin)
timeFrame: 20 weeks
measure: Gut integrity (occludin)
timeFrame: 20 weeks
measure: Gut inflammation
timeFrame: 20 weeks
measure: Gut microbiota profiling
timeFrame: 20 weeks
measure: Short Chain Fatty Acids (SCFA)
timeFrame: 20 weeks
measure: Physical activity
timeFrame: 5, 10, 15, and 20 weeks
measure: Body image
timeFrame: 20 weeks
measure: Depression
timeFrame: 20 weeks
measure: Self-esteem
timeFrame: 20 weeks
measure: Quality of life score
timeFrame: 20 weeks
measure: Morbidity
timeFrame: 5, 10, 15, and 20 weeks
measure: Mortality
timeFrame: 5, 10, 15, and 20 weeks
measure: Wechsler Intelligence Scale for Children score
timeFrame: 20 weeks
measure: Brain Derived Neurotropic Factor level
timeFrame: 20 weeks
measure: Anemia status
timeFrame: 20 weeks
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
state: DKI Jakarta
Study officials:
affiliation: Dep of Nutrition and Human Nutrition Research Center, IMERI, Fac of Medicine Universitas Indonesia
name: Rina Agustina, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.
citation: 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.