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

February 23, 2025 updated by: Prof Rina Agustina, MD, PhD, Indonesia University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
440

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Indonesia
    • DKI Jakarta
      • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
        • Recruiting
        • Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
        • Sub-Investigator:
          • Erfi Prafiantini, MSc
        • Sub-Investigator:
          • Dian N Chandra, PhD
        • Sub-Investigator:
          • Alfi R Putri, MSc
        • Sub-Investigator:
          • Mira Mutiyani, MSc
        • Sub-Investigator:
          • Emy Huriyati, PhD
        • Sub-Investigator:
          • Wahyu Damayanti, MSc
        • Sub-Investigator:
          • Ainun Nisa, SGz
        • Sub-Investigator:
          • Purwo S Rejeki, PhD
        • Sub-Investigator:
          • Lilik Djuari, PhD
        • Sub-Investigator:
          • Adi Pranoto, MKes
        • Sub-Investigator:
          • Fhadilla Amelia, MSc
        • Principal Investigator:
          • Rina Agustina, PhD
        • Contact:
        • Sub-Investigator:
          • Julie Bines, PhD
        • Sub-Investigator:
          • Susan Sawyer, PhD
        • Sub-Investigator:
          • Murdani Abdullah, PhD
        • Sub-Investigator:
          • Dwiana Ocviyanti, PhD
        • Sub-Investigator:
          • Karina R Ekawidyani, PhD
        • Sub-Investigator:
          • Triska S Nindya, PhD
        • Sub-Investigator:
          • Mohammad Juffrie, PhD
        • Sub-Investigator:
          • Dwi Susanti, PhD
        • Sub-Investigator:
          • Alpha F Athiyyah, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 17 years (Child)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intervention
220 overweight/obese adolescents will be given Probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.
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.
Placebo Comparator: Control
220 overweight/obese adolescents will be given placebo probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.
Behavioral: Counselling on healthy eating, physical activity, and psychosocial stimulation
Counselling on healthy eating, physical activity, and psychosocial stimulation.
Dietary supplement: Placebo probiotics
Maltodextrin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
BMI-for-age z-scores (BAZ)
Time Frame: 5, 10, 15, and 20 weeks
Change in BAZ obtain from anthropometric measurements, i.e., weight (kg) and height (m) converted to BMI
5, 10, 15, and 20 weeks
Immunoglobulin G (IgG) specific to SARS-COV-2 titer concentrations
Time Frame: 10 and 20 weeks
Change in IgG specific to SARS-COV-2 titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)
10 and 20 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
α-gut microbiota diversity
Time Frame: 20 weeks
Change in α-diversity measured by 1) Chao1, 2) phylogenetic diversity, and 3) the Shannon index.
20 weeks
β-gut microbiota diversity
Time Frame: 20 weeks
Change in β -diversity: as the variability in community composition (the identity of taxa observed) among samples
20 weeks
Monoclonal antibody affinity against SARS-COV-2
Time Frame: 10 and 20 weeks
Change in equilibrium dissociation constant (KD) of monoclonal antibody against SARS-COV-2 spike protein measured by competitive ELISA
10 and 20 weeks
Secretory Immunoglobulin A (sIgA) specific to SARS-COV-2 titer concentrations
Time Frame: 10 and 20 weeks
Change in sIgA specific to SARS-COV-2 titer concentrations assessed by competitive ELISA
10 and 20 weeks
Dietary quality
Time Frame: 5, 10, 15, and 20 weeks
Change in score of dietary quality assessed by Healthy Eating Index 2015 from 24 hour recalls data
5, 10, 15, and 20 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
SARS-COV-2 infection
Time Frame: 20 weeks
Changes in proportion of symptomatic COVID-19 and positive PCR
20 weeks
Body height
Time Frame: 5, 10, 15, and 20 weeks
Changes in height-for-age z-score by anthropometric measurement
5, 10, 15, and 20 weeks
Abdominal obesity (waist circumference)
Time Frame: 5, 10, 15, and 20 weeks
Changes in waist circumference by anthropometric measurement
5, 10, 15, and 20 weeks
Abdominal obesity (waist-hip ratio)
Time Frame: 5, 10, 15, and 20 weeks
Changes in waist-hip ratio by anthropometric measurement
5, 10, 15, and 20 weeks
Middle upper arm circumference
Time Frame: 5, 10, 15, and 20 weeks
Changes in middle upper arm circumference by anthropometric measurement
5, 10, 15, and 20 weeks
Immunoglobulin M (IgM) against SARS-Cov-2
Time Frame: 10 and 20 weeks
Changes in IgM titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)
10 and 20 weeks
Neutralizing antibody against SARS-Cov-2
Time Frame: 10 and 20 weeks
Changes in total neutralizing antibody titer assessed by Surrogate Virus Neutralization Test (sVNT)
10 and 20 weeks
Gut microbiota profiling
Time Frame: 20 weeks
Changes in composition of gut microbiota assessed by next-generation sequencing (NGS)
20 weeks
Short Chain Fatty Acids (SCFA)
Time Frame: 20 weeks
Change in concentration of the SCFA by gas chromatograph
20 weeks
Physical activity
Time Frame: 5, 10, 15, and 20 weeks
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
Body image
Time Frame: 20 weeks
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
Depression
Time Frame: 20 weeks
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
Self-esteem
Time Frame: 20 weeks
Changes in Rosenberg Self Esteem Scale. The minimum score is 0, and the maximum score is 37. Higher scores mean better outcome.
20 weeks
Quality of life score
Time Frame: 20 weeks
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
Morbidity
Time Frame: 5, 10, 15, and 20 weeks
Type and frequency of illness
5, 10, 15, and 20 weeks
Mortality
Time Frame: 5, 10, 15, and 20 weeks
Type and frequency of illness
5, 10, 15, and 20 weeks
Wechsler Intelligence Scale for Children score
Time Frame: 20 weeks
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
Brain Derived Neurotropic Factor level
Time Frame: 20 weeks
Changes in level of Brain Derived Neurotropic Factor (BDNF) assessed by ELISA
20 weeks
Anemia status
Time Frame: 20 weeks
Changes in hemoglobin concentration
20 weeks
Gut integrity (zonulin)
Time Frame: 20 weeks
Changes in the level of serum zonulin assessed by ELISA and Changes in the level of fecal zonulin assessed by ELISA
20 weeks
Gut integrity (occludin)
Time Frame: 20 weeks
Changes in the level of fecal occludin assessed by ELISA
20 weeks
Gut inflammation
Time Frame: 20 weeks
Changes in concentration of fecal calprotectin assessed by ELISA
20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indonesia University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Melbourne
Gadjah Mada University
Universitas Airlangga
The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rina Agustina, PhD, Dep of Nutrition and Human Nutrition Research Center, IMERI, Fac of Medicine Universitas Indonesia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DIVINE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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