Effects of Probiotic in Treatment of Persistent Diarrhea in Children

NCT05812820 | Completed DMC

• 1 other identifier: 9720109
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

Persistent diarrhea is a common health problem worldwide, particularly in low-income countries. Approximately 3% to 20% of acute diarrhea episodes in children under 5 years of age become persistent diarrhea. Persistent diarrhea causes malnutrition, weight loss, and dehydration, as well as increasing treatment costs and the risk of mortality. One of the main causes of persistent diarrhea is the overgrowth and spread of bacteria, as well as viral infections that can disrupt the balance of microorganisms in the gut. Antibiotics are effective in treating bacterial infections that cause persistent diarrhea in children, but not against viral or parasitic infections. Overuse of antibiotics can lead to the growth of antibiotic-resistant bacteria, which poses a significant public health concern. Probiotics play a vital role in maintaining a healthy balance. Bacillus probiotic strains have an advantage over Lactobacillus probiotics as they can form spores that resist environmental stressors like heat, acid, and bile. This makes them more likely to survive the harsh conditions of the digestive tract and provide health benefits by reaching the intestines intact. Here, the investigators propose high-dose Bacillus spore probiotic supplementation as a potential solution for treating patients with persistent diarrhea. The aim of the study is to assess the efficacy of two types of Bacillus probiotics which conclude LiveSpo CLAUSY (2 billion B. clausii) and LiveSpo DIA 30 (5 billion B. subtilis, B. clausii and B. coagulans) in supporting the treatment of children with persistent diarrhea. Study Population: sample size is 150 patients and 30 healthy children. The study is carried out at Vietnam National Children's Hospital. Description of Study Intervention: Totally 150 eligible patients are divided randomly into 3 groups (n = 50/group each): Patients in the Control group received the routine treatment and 2-3 times/day RO water while the patients in the probiotics group received 2-3 times/day LiveSpo DIA 30 or LiveSpo CLAUSY in addition to the same standard of care treatment. The standard treatment regimen is 5-9 days but can be extended further depending on the severity of the patient. Healthy children are grouped into the "Healthy" group solely for the purpose of comparing the microbiota between healthy children with those patients before and after treatment. Therefore, the Healthy group does not receive any intervention. Study duration: 18 months

Conditions

Diarrhea

Keywords

Bacillus spore; Bacterial; Children; Gut microbiota; Persistent diarrhea; Viruses

Outcome Measures

Primary Outcomes (1)

• Changes in days of treatment for typical symptoms of persistent diarrhea

  Changes in days of treatment for typical symptoms of persistent diarrhea, including: * the frequency of bowel movements per day (times/day) * the presence of mucus in stool (2 - lots of mucus, 1 - less mucus, 0 - no mucus) * the Bristol Stool Score ( 1 - Type 1, 2 - Type 2, 3 - Type 3, 4 - Type 4, 5 - Type 5A, 6 - Type 5B)

  Day 0 to Day 12

Secondary Outcomes (5)

• Changes in presence of white blood cells and red blood cells by stool microscopy

  Day 3 and Day 5 compared to Day 0

• Changes in Intestinal microbiota

  Day 3 or/and Day 7 compared to Day 0

• Changes in cytokines levels of blood samples

  Day 5 compared to Day 0

• Changes in IgA levels in both stool and blood samples

  Day 5 compared to Day 0

• Change the stool pH values

  Day 3 and Day 5 compared to Day 0

Study Arms (3)

Control

PLACEBO COMPARATOR

Control group receives the routine treatment and uses distilled water (RO) water Routine treatment at Department of Gastroenterology, Vietnam National Children's Hospital is as follows: * Antibiotics: oral (e.g. Zithromax® or Ciprofloxacin®) or intervention (ceftriaxone®, Ciprofloxacin®, Metronidazole®, Vancomycin®) drugs. * Oral rehydration Solution: Oremute * Zinc gluconate

Other: RO

DIA30

EXPERIMENTAL

DIA 30 group receives the routine treatment and uses distilled water plus B. subtilis, B. clausii and B. coagulans at 5 billion CFU/5 mL (LiveSpo® DIA 30) Routine treatment at Department of Gastroenterology, Vietnam National Children's Hospital is as follows: * Antibiotics: oral (e.g. Zithromax® or Ciprofloxacin®) or intervention (ceftriaxone®, Ciprofloxacin®, Metronidazole®, Vancomycin®) drugs. * Oral rehydration Solution: Oremute * Zinc gluconate

Combination Product: LiveSpo DIA30

CLAUSY

EXPERIMENTAL

CLAUSY group receives the routine treatment and uses distilled water plus B. clausii at 2 billion CFU/5 mL (LiveSpo® CLAUSY) Routine treatment at Department of Gastroenterology, Vietnam National Children's Hospital is as follows: * Antibiotics: oral (e.g. Zithromax® or Ciprofloxacin®) or intervention (ceftriaxone®, Ciprofloxacin®, Metronidazole®, Vancomycin®) drugs. * Oral rehydration Solution: Oremute * Zinc gluconate

Combination Product: LiveSpo CLAUSY

Interventions

LiveSpo DIA30 COMBINATION_PRODUCT

LiveSpo® DIA 30 has a registration number: 6547/2019/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam

DIA30

LiveSpo CLAUSY COMBINATION_PRODUCT

LiveSpo® CLAUSY has a registration number: 4071/2021/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam

CLAUSY

RO OTHER

Aquafina's distilled water and reverse osmosis (RO) water, produce by PepsiCo, have both obtained ISO 9001:2015 and ISO 22000:2018 certifications, which are internationally recognized standards for quality management and food safety management systems, respectively. The RO water ampoules are produced using a similar process as the LIVESPO DIA30/CLAUSY but contain 5ml of high-quality distilled water from Aquafina in an opaque plastic bottle

Control

Eligibility Criteria

• Age: 2 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Patients who are between 2 months and 24 months old
• Have loose or unusual watery stools more than 3 times per day, lasting between 14 and 30 days
• Parents of the pediatric patient agree to participate in the study, explain and sign the research consent form

You may not qualify if:

• The patient had any systemic illness other than diarrhea on admission.
• Patient has any systemic complications during treatment.

Sponsors & Collaborators

• National Children's Hospital, Vietnam: lead

Study Sites (1)

Department of Gastroenterology, Vietnam National Children's Hospital

Hanoi, Vietnam, 100000, Vietnam

Location

Related Publications (13)

• Sarker SA, Ahmed T, Brussow H. Persistent diarrhea: a persistent infection with enteropathogens or a gut commensal dysbiosis? Environ Microbiol. 2017 Oct;19(10):3789-3801. doi: 10.1111/1462-2920.13873. Epub 2017 Sep 14.

  PMID: 28752952 BACKGROUND

• Fan Q, Yi M, Liu H, Wang Y, Li X, Yuan J, Wang L, Hou B, Li M. The Impact of Age and Pathogens Type on the Gut Microbiota in Infants with Diarrhea in Dalian, China. Can J Infect Dis Med Microbiol. 2020 Nov 30;2020:8837156. doi: 10.1155/2020/8837156. eCollection 2020.

  PMID: 33312314 BACKGROUND

• Bandsma RHJ, Sadiq K, Bhutta ZA. Persistent diarrhoea: current knowledge and novel concepts. Paediatr Int Child Health. 2019 Feb;39(1):41-47. doi: 10.1080/20469047.2018.1504412. Epub 2018 Aug 6.

  PMID: 30079818 BACKGROUND

• Szajewska H, Kolodziej M. Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults. Aliment Pharmacol Ther. 2015 Nov;42(10):1149-57. doi: 10.1111/apt.13404. Epub 2015 Sep 13.

  PMID: 26365389 BACKGROUND

• Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar 27;157(1):121-41. doi: 10.1016/j.cell.2014.03.011.

  PMID: 24679531 BACKGROUND

• Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10.

  PMID: 24912386 BACKGROUND

• Ugboko HU, Nwinyi OC, Oranusi SU, Oyewale JO. Childhood diarrhoeal diseases in developing countries. Heliyon. 2020 Apr 13;6(4):e03690. doi: 10.1016/j.heliyon.2020.e03690. eCollection 2020 Apr.

  PMID: 32322707 BACKGROUND

• Abba K, Sinfield R, Hart CA, Garner P. Pathogens associated with persistent diarrhoea in children in low and middle income countries: systematic review. BMC Infect Dis. 2009 Jun 10;9:88. doi: 10.1186/1471-2334-9-88.

  PMID: 19515227 BACKGROUND

• Olvera-Rosales LB, Cruz-Guerrero AE, Ramirez-Moreno E, Quintero-Lira A, Contreras-Lopez E, Jaimez-Ordaz J, Castaneda-Ovando A, Anorve-Morga J, Calderon-Ramos ZG, Arias-Rico J, Gonzalez-Olivares LG. Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods. 2021 Jun 2;10(6):1261. doi: 10.3390/foods10061261.

  PMID: 34199351 BACKGROUND

• Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019 Apr 30;4(4):CD004827. doi: 10.1002/14651858.CD004827.pub5.

  PMID: 31039287 BACKGROUND

• Tridip K. Das, Shrabani Pradhan, Sudipta Chakrabarti, Keshab Chandra Mondal, Kuntal Ghosh, Current status of probiotic and related health benefits, Applied Food Research, Volume 2, Issue 2, 2022, 100185, ISSN 2772-5022

  BACKGROUND

• Dang HT, Phung TTB, Tran DM, Bui ATP, Vu YH, Luong MT, Nguyen HM, Trinh HT, Vo HTN, Nguyen TTT, Nguyen AH, Tung PD, Tran LH, Van Nguyen AT. High-dose multi-strain Bacillus probiotics enhance treatment and reduce antibiotic usage in children with persistent diarrhea through immune and microbiota modulation. Sci Rep. 2025 Aug 18;15(1):30231. doi: 10.1038/s41598-025-15199-y.

  PMID: 40826150 DERIVED

• Dang HT, Tran DM, Phung TTB, Bui ATP, Vu YH, Luong MT, Nguyen HM, Trinh HT, Nguyen TT, Nguyen AH, Van Nguyen AT. Promising clinical and immunological efficacy of Bacillus clausii spore probiotics for supportive treatment of persistent diarrhea in children. Sci Rep. 2024 Mar 18;14(1):6422. doi: 10.1038/s41598-024-56627-9.

  PMID: 38494525 DERIVED

Related Links

• Diarrheal disease

MeSH Terms

Conditions

Diarrhea; Virus Diseases

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections

Study Officials

• Dang T Ha, MD

  Department of Gastroenterology, Vietnam National Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: LiveSpo DIA30, LiveSpo CLAUSY, and RO water are indistinguishable in terms of smell. However, due to the opaque plastic container of the LiveSpo product suspension, the color and turbidity of the suspension are unrecognizable to investigators, except for the Principal Investigator (PI), analyzer, nurses, patient's parents, and patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Head of Gastrointestinal Department

Model Details: A randomized, double-blind, controlled clinical trial

Study Record Dates

• First Submitted: March 25, 2023
• First Posted: April 14, 2023
• Study Start: July 1, 2022
• Primary Completion: December 25, 2023
• Study Completion: November 25, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a study protocol, informed consent form (ICF), clinical study report (CSR). For more information or to submit a request, please contact clinicaltrial.probiotics@gmail.com

Locations

VN (1)