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).
| Title: | 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). |
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| Authors: | Agustina R; Department of Nutrition, Faculty of Medicine - Dr. Cipto Mangunkusumo General Hospital, Universitas Indonesia, Jakarta, Indonesia r.agustina@ui.ac.id dr.rinaagustina@gmail.com.; Human Nutrition Research Center, Indonesian Medical Education and Research Institute (HNRC-IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Ekawidyani KR; Doctoral Study Program in Nutrition, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Department of Community Nutrition, Faculty of Human Ecology, IPB University, Bogor, West Java, Indonesia.; Mutiyani M; Doctoral Study Program in Nutrition, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Department of Nutrition, Poltekkes Kemenkes Bandung, Bandung, West Java, Indonesia.; Prafiantini E; Department of Nutrition, Faculty of Medicine - Dr. Cipto Mangunkusumo General Hospital, Universitas Indonesia, Jakarta, Indonesia.; Human Nutrition Research Center, Indonesian Medical Education and Research Institute (HNRC-IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Nindya TS; Doctoral Study Program in Nutrition, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Department of Nutrition, Faculty of Public Health, Universitas Airlangga, Surabaya, East Java, Indonesia.; Damayanti W; Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.; Rejeki PS; Physiology Division, Department of Medical Physiology and Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.; Djuari L; Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.; Huriyati E; Department of Nutrition and Health, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia.; Bines JE; Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.; Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital Research Institute, Parkville, Victoria, Australia.; Murdoch Children's Research Institute, Parkville, Victoria, Australia.; Juffrie M; Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. |
| Source: | BMJ open [BMJ Open] 2025 Apr 02; Vol. 15 (4), pp. e087934. Date of Electronic Publication: 2025 Apr 02. |
| Publication Type: | Journal Article; Clinical Trial Protocol |
| Language: | English |
| Journal Info: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BMJ Publishing Group Ltd, 2011- |
| MeSH Terms: | Probiotics*/therapeutic use ; Probiotics*/administration & dosage ; COVID-19*/prevention & control ; COVID-19*/immunology ; Nutritional Status* ; Pediatric Obesity*; Indonesia/epidemiology ; SARS-CoV-2/immunology ; Humans ; Adolescent ; Randomized Controlled Trials as Topic ; Child ; Female ; Male ; Overweight ; Antibody Formation ; Gastrointestinal Microbiome |
| Abstract: | Introduction: During the pandemic, overweight and obese adolescents were at a higher risk of COVID-19 infection. Indonesia's government has implemented prevention programmes and immunisation; however, the rise in SARS-CoV-2 infections among adolescents is exacerbated by low-quality diet and lifestyle habits. Also, the vaccine programme is not prioritised in this population. To address this, a solution involves providing probiotics and counselling on healthy lifestyle habits to improve diet and immunity. Therefore, we designed a protocol for a randomised controlled trial with a 20-week intervention to investigate the effect of probiotics supplementation and counselling on healthy lifestyle habits, including healthy eating and physical activity, and psychosocial stimulation, on nutritional status and antibody response against SARS-CoV-2 in this group.; Methods and Analysis: This clinical trial aims to investigate the effects of probiotic supplementation on healthy overweight and obese adolescents. The study will involve 440 adolescents aged 12-17 living in Jakarta, Surabaya or Yogyakarta for at least 6 months and have completed at least two doses of the COVID-19 vaccine. The intervention group will receive daily probiotic supplementation of three strains, including Bifidobacterium animalis subsp. Lactis (BB-12), Lactobacillus acidophilus (LA-5) and Lactobacillus rhamnosus (LGG), at the level of 109-1010 colony-forming units for 20 weeks, while the control group will receive a placebo. Both groups will receive weekly counselling on healthy eating habits, physical activity and psychosocial stimulation. The primary outcomes will be changes in the body mass index for age z-score and IgG specific to SARS-CoV-2 titre concentrations between groups. The secondary outcomes will include changes in secretory IgA specific to SARS-CoV-2 titre concentrations, monoclonal antibodies against SARS-CoV-2 spike protein, gut microbiota diversity and the score of Healthy Eating Index 2015.; Ethics and Dissemination: The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia-Cipto Mangunkusumo Hospital (KET 763/UN2.F1/ETIK/PPM.00.02/2022: 1 August 2022). The study results will be disseminated in open-access international journals, scientific meetings and conferences with stakeholders.; Trial Registration Number: The study has been registered at https://clinicaltrials.gov with identifier number NCT05623007.; (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.) |
| Competing Interests: | Competing interests: None declared. |
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| Contributed Indexing: | Keywords: Adolescent; Obesity; Overweight; Probiotic; Randomized Controlled Trial; SARS-CoV-2 Infection |
| Molecular Sequence: | ClinicalTrials.gov NCT05623007 |
| Entry Date(s): | Date Created: 20250403 Date Completed: 20250403 Latest Revision: 20250602 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11969610 |
| DOI: | 10.1136/bmjopen-2024-087934 |
| PMID: | 40180370 |
| Database: | MEDLINE |
Journal Article; Clinical Trial Protocol