search
Back to results

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

Primary Purpose

Health Behavior, Child Development, Adolescent Obesity

Status
Recruiting
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Probiotics
Counselling on healthy eating, physical activity, and psychosocial stimulation
Placebo probiotics
Sponsored by
Indonesia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Health Behavior focused on measuring adolescent, probiotics, COVID-19, overweight, obese

Eligibility Criteria

12 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

  • Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas IndonesiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

BMI-for-age z-scores (BAZ)
Change in BAZ obtain from anthropometric measurements, i.e., weight (kg) and height (m) converted to BMI
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)

Secondary Outcome Measures

α-gut microbiota diversity
Change in α-diversity measured by 1) Chao1, 2) phylogenetic diversity, and 3) the Shannon index.
β-gut microbiota diversity
Change in β -diversity: as the variability in community composition (the identity of taxa observed) among samples
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
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
Dietary quality
Change in score of dietary quality assessed by Healthy Eating Index 2015 from 24 hour recalls data

Full Information

First Posted
October 31, 2022
Last Updated
November 17, 2022
Sponsor
Indonesia University
Collaborators
Gadjah Mada University, Universitas Airlangga, University of Melbourne, The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia
search

1. Study Identification

Unique Protocol Identification Number
NCT05623007
Brief Title
Dietary Modulation of Gut Microbiota in Overweight/Obese Adolescents and COVID-19 Infection
Acronym
DIVINE
Official Title
Dietary Modulation of Gut Microbiota on Nutritional Status and COVID-19 Infection in Adolescents: Gut-Lung-Axis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
November 2, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
Collaborators
Gadjah Mada University, Universitas Airlangga, University of Melbourne, The Indonesia Endowment Funds for Education, Ministry of Finance Indonesia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Health Behavior, Child Development, Adolescent Obesity
Keywords
adolescent, probiotics, COVID-19, overweight, obese

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Participant, Enumerator, Investigator, Outcomes Assessor) Participant, enumerator, investigator, and outcomes assessor do not know which one is the intervention product or placebo.
Allocation
Randomized
Enrollment
440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
220 overweight/obese adolescents will be given Probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
220 overweight/obese adolescents will be given placebo probiotics and counselling on healthy eating, physical activity, and psychosocial stimulation.
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotics
Intervention Description
Combination of 3 probiotic strains: Lactobacillus rhamnosus (LGG), Bifidobacterium animalis subsp. lactis (BB-12), and Lactobacillus acidophilus (LA-5)
Intervention Type
Behavioral
Intervention Name(s)
Counselling on healthy eating, physical activity, and psychosocial stimulation
Intervention Description
Counselling on healthy eating, physical activity, and psychosocial stimulation.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo probiotics
Intervention Description
Maltodextrin
Primary Outcome Measure Information:
Title
BMI-for-age z-scores (BAZ)
Description
Change in BAZ obtain from anthropometric measurements, i.e., weight (kg) and height (m) converted to BMI
Time Frame
5, 10, 15, and 20 weeks
Title
Immunoglobulin G (IgG) specific to SARS-COV-2 titer concentrations
Description
Change in IgG specific to SARS-COV-2 titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)
Time Frame
10 and 20 weeks
Secondary Outcome Measure Information:
Title
α-gut microbiota diversity
Description
Change in α-diversity measured by 1) Chao1, 2) phylogenetic diversity, and 3) the Shannon index.
Time Frame
20 weeks
Title
β-gut microbiota diversity
Description
Change in β -diversity: as the variability in community composition (the identity of taxa observed) among samples
Time Frame
20 weeks
Title
Monoclonal antibody affinity against SARS-COV-2
Description
Change in equilibrium dissociation constant (KD) of monoclonal antibody against SARS-COV-2 spike protein measured by competitive ELISA
Time Frame
10 and 20 weeks
Title
Secretory Immunoglobulin A (sIgA) specific to SARS-COV-2 titer concentrations
Description
Change in sIgA specific to SARS-COV-2 titer concentrations assessed by competitive ELISA
Time Frame
10 and 20 weeks
Title
Dietary quality
Description
Change in score of dietary quality assessed by Healthy Eating Index 2015 from 24 hour recalls data
Time Frame
5, 10, 15, and 20 weeks
Other Pre-specified Outcome Measures:
Title
SARS-COV-2 infection
Description
Changes in proportion of symptomatic COVID-19 and positive PCR
Time Frame
20 weeks
Title
Body height
Description
Changes in height-for-age z-score by anthropometric measurement
Time Frame
5, 10, 15, and 20 weeks
Title
Abdominal obesity (waist circumference)
Description
Changes in waist circumference by anthropometric measurement
Time Frame
5, 10, 15, and 20 weeks
Title
Abdominal obesity (waist-hip ratio)
Description
Changes in waist-hip ratio by anthropometric measurement
Time Frame
5, 10, 15, and 20 weeks
Title
Middle upper arm circumference
Description
Changes in middle upper arm circumference by anthropometric measurement
Time Frame
5, 10, 15, and 20 weeks
Title
Immunoglobulin M (IgM) against SARS-Cov-2
Description
Changes in IgM titer concentrations assessed by electro chemiluminescence immunoassay (ECLIA)
Time Frame
10 and 20 weeks
Title
Neutralizing antibody against SARS-Cov-2
Description
Changes in total neutralizing antibody titer assessed by Surrogate Virus Neutralization Test (sVNT)
Time Frame
10 and 20 weeks
Title
Gut integrity
Description
Changes in level of zonulin assessed by ELISA
Time Frame
10 and 20 weeks
Title
Gut microbiota profiling
Description
Changes in composition of gut microbiota assessed by next-generation sequencing (NGS)
Time Frame
20 weeks
Title
Short Chain Fatty Acids (SCFA)
Description
Change in concentration of the SCFA by gas chromatograph
Time Frame
20 weeks
Title
Physical activity
Description
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.
Time Frame
5, 10, 15, and 20 weeks
Title
Body image
Description
Changes in Body Shape Questionnaire-34 (BSQ-34) score. The minimum score is 34, and the maximum is 204. Higher score means worse outcome
Time Frame
20 weeks
Title
Depression
Description
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.
Time Frame
20 weeks
Title
Self-esteem
Description
Changes in Rosenberg Self Esteem Scale. The minimum score is 0, and the maximum score is 37. Higher scores mean better outcome.
Time Frame
20 weeks
Title
Quality of life score
Description
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.
Time Frame
20 weeks
Title
Morbidity
Description
Type and frequency of illness
Time Frame
5, 10, 15, and 20 weeks
Title
Mortality
Description
Type and frequency of illness
Time Frame
5, 10, 15, and 20 weeks
Title
Wechsler Intelligence Scale for Children score
Description
Changes in Wechsler Intelligence Scale for Children (WISC). The minimum score is 70, and the maximum score is 159. Higher scores mean better outcome.
Time Frame
20 weeks
Title
Brain Derived Neurotropic Factor level
Description
Changes in level of Brain Derived Neurotropic Factor (BDNF) assessed by ELISA
Time Frame
20 weeks
Title
Anemia status
Description
Changes in hemoglobin concentration
Time Frame
20 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rina Agustina, PhD
Phone
+622129189160
Ext
201052
Email
dr.rinaagustina@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Rahyussalim Rahyussalim, PhD
Phone
+62 21 291 891 60
Ext
201908
Email
manajer.riset.fkui1@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rina Agustina, PhD
Organizational Affiliation
Human Nutrition Research Center, IMERI; Dep of Nutrition, Fac.of Medicine UI
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
City
Jakarta Pusat
State/Province
DKI Jakarta
ZIP/Postal Code
10430
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rina Agustina, PhD
Phone
+6221 2912477
First Name & Middle Initial & Last Name & Degree
Rina Agustina, PhD
First Name & Middle Initial & Last Name & Degree
Julie Bines, Prof
First Name & Middle Initial & Last Name & Degree
Susan Sawyer, Prof
First Name & Middle Initial & Last Name & Degree
Murdani Abdullah, Prof
First Name & Middle Initial & Last Name & Degree
Erfi Prafianti, MSc
First Name & Middle Initial & Last Name & Degree
Dwiana Ocviyanti, Prof
First Name & Middle Initial & Last Name & Degree
Karina R Ekawidyani, MSc
First Name & Middle Initial & Last Name & Degree
Dian N Chandra, PhD
First Name & Middle Initial & Last Name & Degree
Okky L Sari, MPH
First Name & Middle Initial & Last Name & Degree
Deviana S Siregar, MSc
First Name & Middle Initial & Last Name & Degree
Alfi R Putri, MSc
First Name & Middle Initial & Last Name & Degree
Triska S Nindya, MPH
First Name & Middle Initial & Last Name & Degree
Mira Mutiyani, MSc
First Name & Middle Initial & Last Name & Degree
Rizqy A Pamungkas, SGz
First Name & Middle Initial & Last Name & Degree
Juffrie Juffrie, Prof
First Name & Middle Initial & Last Name & Degree
Emy Huriyati, PhD
First Name & Middle Initial & Last Name & Degree
Wahyu Damayanti, MSc
First Name & Middle Initial & Last Name & Degree
Ainun Nisa, SGz
First Name & Middle Initial & Last Name & Degree
Purwo S Rejeki, PhD
First Name & Middle Initial & Last Name & Degree
Lilik Djuari, PhD
First Name & Middle Initial & Last Name & Degree
Dwi Susanti, MPH
First Name & Middle Initial & Last Name & Degree
Adi Pranoto, MKes
First Name & Middle Initial & Last Name & Degree
Fhadilla Amelia, MSc

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29559977
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.
Results Reference
background
PubMed Identifier
33495676
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.
Results Reference
background
PubMed Identifier
22492764
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.
Results Reference
background
PubMed Identifier
31703257
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs