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

Health Behavior Clinical Trial

— DIVINE  

Official title:

Dietary Modulation of Gut Microbiota on Nutritional Status and COVID-19 Infection in Adolescents: Gut-Lung-Axis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05623007
• Other study ID #: DIVINE
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2022
• Est. completion date: November 2, 2025

Study information

• Verified date: November 2022
• Source: Indonesia University
• Contact: Rina Agustina, PhD
• Phone: +622129189160
• Email: dr.rinaagustina[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: November 2, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adolescent Obesity
• Child Development
• COVID-19
• Health Behavior
• Pediatric Obesity

Intervention

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

Behavioral:
• Counselling on healthy eating, physical activity, and psychosocial stimulation
Counselling on healthy eating, physical activity, and psychosocial stimulation.

Dietary Supplement:
• Placebo probiotics
Maltodextrin

Locations

Country	Name	City	State
Indonesia	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

Sponsors (5)

Lead Sponsor	Collaborator
Indonesia University	Gadjah Mada University, The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia, Universitas Airlangga, University of Melbourne

Country where clinical trial is conducted

Indonesia, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SARS-COV-2 infection	Changes in proportion of symptomatic COVID-19 and positive PCR	20 weeks
Other	Body height	Changes in height-for-age z-score by anthropometric measurement	5, 10, 15, and 20 weeks
Other	Abdominal obesity (waist circumference)	Changes in waist circumference by anthropometric measurement	5, 10, 15, and 20 weeks
Other	Abdominal obesity (waist-hip ratio)	Changes in waist-hip ratio by anthropometric measurement	5, 10, 15, and 20 weeks
Other	Middle upper arm circumference	Changes in middle upper arm circumference by anthropometric measurement	5, 10, 15, and 20 weeks
Other	Immunoglobulin M (IgM) against SARS-Cov-2	Changes in IgM titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)	10 and 20 weeks
Other	Neutralizing antibody against SARS-Cov-2	Changes in total neutralizing antibody titer assessed by Surrogate Virus Neutralization Test (sVNT)	10 and 20 weeks
Other	Gut integrity	Changes in level of zonulin assessed by ELISA	10 and 20 weeks
Other	Gut microbiota profiling	Changes in composition of gut microbiota assessed by next-generation sequencing (NGS)	20 weeks
Other	Short Chain Fatty Acids (SCFA)	Change in concentration of the SCFA by gas chromatograph	20 weeks
Other	Physical activity	Changes in International Physical Activity Questionnaire for Adolescent (IPAQ-A) score, the minimum is 0 metabolic equivalents of task (MET) minutes/week, and the maximum score is 3000 MET minutes/week. Higher score means better outcome.	5, 10, 15, and 20 weeks
Other	Body image	Changes in Body Shape Questionnaire-34 (BSQ-34) score. The minimum score is 34, and the maximum is 204. Higher score means worse outcome	20 weeks
Other	Depression	Changes in Patient Health Questionnaire for Adolescents (PHQ-A) score. The minimum score is 0, and the maximum is 27. Higher scores mean worse outcome.	20 weeks
Other	Self-esteem	Changes in Rosenberg Self Esteem Scale. The minimum score is 0, and the maximum score is 37. Higher scores mean better outcome.	20 weeks
Other	Quality of life score	Changes in the score of Youth Quality of Life for adolescents-Research version (YQOL-R). The minimum score is 0, and the maximum score is 100. Higher scores mean better outcome.	20 weeks
Other	Morbidity	Type and frequency of illness	5, 10, 15, and 20 weeks
Other	Mortality	Type and frequency of illness	5, 10, 15, and 20 weeks
Other	Wechsler Intelligence Scale for Children score	Changes in Wechsler Intelligence Scale for Children (WISC). The minimum score is 70, and the maximum score is 159. Higher scores mean better outcome.	20 weeks
Other	Brain Derived Neurotropic Factor level	Changes in level of Brain Derived Neurotropic Factor (BDNF) assessed by ELISA	20 weeks
Other	Anemia status	Changes in hemoglobin concentration	20 weeks
Primary	BMI-for-age z-scores (BAZ)	Change in BAZ obtain from anthropometric measurements, i.e., weight (kg) and height (m) converted to BMI	5, 10, 15, and 20 weeks
Primary	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)	10 and 20 weeks
Secondary	a-gut microbiota diversity	Change in a-diversity measured by 1) Chao1, 2) phylogenetic diversity, and 3) the Shannon index.	20 weeks
Secondary	ß-gut microbiota diversity	Change in ß -diversity: as the variability in community composition (the identity of taxa observed) among samples	20 weeks
Secondary	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	10 and 20 weeks
Secondary	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	10 and 20 weeks
Secondary	Dietary quality	Change in score of dietary quality assessed by Healthy Eating Index 2015 from 24 hour recalls data	5, 10, 15, and 20 weeks