Efficacy of Probiotics (LiveSpo Navax) in Preventing Respiratory Diseases in Children

Respiratory Disease Clinical Trial

Official title:

Efficacy of Physiological Saline and Probiotics (LiveSpo Navax) in Preventing Respiratory Diseases in Children Aged 2-6, in Son Tay Province, Hanoi

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06148194
• Other study ID #: TNLS.2023.NP
• Secondary ID: No. 202/HDDD-VKC
• Status: Recruiting
• Phase: N/A
• Start date: January 2, 2024
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Anabio R&D
• Contact: Thu TH Nguyen, Assoc. Prof.
• Phone: (84) 903211266
• Email: nguyenhoaithu[@]hmu.edu.vn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute respiratory infections are common diseases worldwide with the highest incidence and mortality rates, especially among children. Currently, the prevention of acute respiratory infections in children still faces certain limitations. Although there is a vaccine available for influenza, there are no vaccines yet for RSV and adenovirus in children, and influenza vaccination needs to be repeated annually to achieve optimal effectiveness. Therefore, maintaining respiratory and throat hygiene is essential for both treatment and prevention, ensuring respiratory health for children and reducing the risk of bacterial co-infections. In recent years, preventive strategies for respiratory inflammation have garnered increasing attention, with probiotics being shown to have the potential to support treatment and prevention & reduce the risk of recurrent respiratory infections, thus decreasing reliance on antibiotics. Here, the investigators propose that direct nasal spraying of probiotics may be safe and effective in preventing respiratory diseases.

The aim of the study is to evaluate the effectiveness of two types of nasal- praying Bacillus probiotics including LiveSpo Navax (1 billion/mL x 30 mL B. subtilis and B. clausii) and LiveSpo Navax Kid (0.6 billion/mL x 30 mL B. subtilis and B. clausii) in preventing respiratory diseases. Study Population: The sample size is 600. Description of Sites: The study is conducted at preschools in Son Tay Province, Hanoi, Vietnam.

Description of Study Intervention: A total of 600 eligible children are randomly divided into three groups (n = 200/group each). Children in the Control group received 0.9% NaCl physiological saline twice daily (morning and afternoon), with 2 sprays in each nostril and 2 sprays in the throat each time (totally 6 sprays each time), continuously for four weeks. Children in the Probiotic 1 group receive LiveSpo Navax product, and children in the Probiotic 2 group receive LiveSpo Navax Kid, with the same dosage and frequency as the Control group.

Study Duration: 12 months.

Description:

Acute respiratory infections are common diseases worldwide with the highest incidence and mortality rates, especially among children. Vietnam is one of the 15 countries with the highest pneumonia rates in the world, with an estimated 2.9 million cases occurring annually. The age group most susceptible to acute respiratory infections is children under 5 years old, especially bronchiolitis, which often occurs in children under 2 years old. The incidence of acute respiratory infections varies with the seasons, with the highest prevalence of viral respiratory infections typically occurring during the winter and spring. In tropical regions, acute respiratory infections are more common during the rainy months, while in temperate regions, they are more prevalent during the winter months. Approximately 30-60% of outpatient visits for medical care are due to acute respiratory infections.

Currently, the prevention of acute respiratory infections in children still faces certain limitations. Although there is a vaccine available for influenza, there are no vaccines yet for RSV and adenovirus in children, and influenza vaccination needs to be repeated annually to achieve optimal effectiveness. Therefore, maintaining respiratory and throat hygiene is essential for both treatment and prevention, ensuring respiratory health for children and reducing the risk of bacterial co-infections. Here, the investigators propose that direct nasal spraying of probiotics may be a safe and effective method for preventing respiratory diseases.

The objective of this study is to investigate the safety and preventive effects of two types of nasal-spraying Bacillus probiotics: LiveSpo Navax (1 billion/mL x 30 mL B. subtilis and B. clausii) and LiveSpo Navax Kid (containing 0.6 billion/mL x 30 mL B. subtilis and B. clausii) in preventing respiratory diseases in healthy children attending preschools. The investigators will evaluate the preventive efficacy in terms of reducing the number of respiratory disease episodes and the number of courses of antibiotics in children after 2 weeks and 4 weeks of using LiveSpo Navax and LiveSpo Navax Kid.

A randomized, double-blind, and controlled clinical trial will be conducted. Parents of the will be required to provide various information about their children, including their full names, sex, ages, respiratory infection history, and history of antibiotic use... After obtaining informed consent, 600 children will be randomly assigned to three groups (n = 200/group): the control group (referred to as the "Control" group) will receive 0.9% NaCl physiological saline, the experimental group 1 (referred to as the "Probiotic 1" group) will receive the probiotic LiveSpo Navax product, and the experimental group 2 (referred to as the "Probiotic 2" group) will receive the probiotic LiveSpo Navax Kid. Children will be provided with coded nasal sprays in blinded samples to ensure the objectivity of the study. Clinical examinations and monitoring will be conducted after 2 weeks and 4 weeks of the experiment. Nasopharyngeal samples will be collected at the same time as the clinical examinations to assess the presence of probiotic spores in the children's nasal mucosa. During the trial, children's typical clinical symptoms of respiratory tract infections are monitored, including runny nose, stuffy nose, sneezing, sore throat, cough, and fatigue. Data is collected on the number of cold or illness episodes, the average duration of each illness episode, the number of days absent from school, and medication history after 2 weeks and 4 weeks of participating in the study. The children's health conditions are observed by caregivers, and the information is recorded in medical records. During this study, parents or caregivers are asked to refrain from giving their children other probiotics, whether via nasal spray or oral administration, and to avoid cleaning their children's noses with other 0.9% NaCl physiological saline sprayers. Data collection and statistical analysis will involve collecting individual medical records and systematically organizing the children's information into a dataset.

The prevention efficacy of LiveSpo Navax product (Probiotic 1 group) and LiveSpo Navax Kid (Probiotic 2 group) is evaluated and compared to 0.9% NaCl physiological saline (Control group) based on the following clinical and survey criteria: (i) reduction in the percentage (%) of children with respiratory infections; (ii) reduction in the number of colds, illnesses, or respiratory tract infections in children; (iii) reduction in the duration of medication usage and the number of medication episodes in the treatment of respiratory diseases. Tabular analysis is performed on dichotomous variables using the χ2 test or Fisher's exact test when the expected value of any cell is below five. Continuous variables are compared using either the t-test or the Mann-Whitney test when the data is not normally distributed. Statistical and graphical analyses are conducted using GraphPad Prism v8.4.3 software (GraphPad Software, CA, USA). The significance level for all analyses is set at p < 0.05.

Detection of B. subtilis ANA4 and B. clausii ANA39 in nasopharyngeal samples was conducted at 2 weeks and 4 weeks using real-time PCR with SYBR Green following the ISO 17025:2017 guidelines. This testing was performed at the Spobiotic Research Center.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years to 6 Years

Eligibility

Inclusion Criteria:

• Children (male/female) aged from 2 to 6 years, currently attending a preschool.

• Parents of the pediatric agree to participate in the study, explain, and sign the research consent form.

Exclusion Criteria:

• Children with a history of nasal reconstructive surgery, nasal ulcers, or nasal polyps.

• Children with a history of congenital immunodeficiency or infectious diseases (e.g., HIV).

• Children who regularly use products that may affect the research outcomes (e.g., immunosuppressive/immunostimulant drugs, pain relievers/anti-inflammatory drugs, anti-cough/expectorant drugs, antihistamines, or other probiotics) within 4 weeks before the start of the study.

• Children with co-morbidities that affect cognition and perception.

Related Conditions & MeSH terms

• Respiration Disorders
• Respiratory Disease
• Respiratory Infections in Children
• Respiratory Tract Diseases
• Respiratory Tract Infections

Intervention

Drug:
• 0.9% NaCl physiological saline
Nasal-spraying 0.9% NaCl physiological saline is prepared by extracting 5 mL from 0.9% NaCl intravenous infusion 500 mL PP bottle (B.Braun, Germany, product declaration No. Nasal-spraying 0.9% NaCl physiological saline is prepared by extracting 30 mL from 0.9% NaCl intravenous infusion 500 mL PP bottle (B.Braun, Germany, product declaration No. VD-32732-19), and then pouring it into the same opaque plastic spraying 30 mL-bottle that is used for probiotic 1 and 2.

Combination Product:
• Probiotic 1
In Vietnam, LiveSpo Navax is manufactured as a Class-A medical device (Product declaration: No. 210001337/PCBA-HN) in accordance with manufacturing standards approved by the Hanoi Health Department, Ministry of Health, Vietnam (Certificate No. YT117-19), and ISO 13485:2016. LiveSpo Navax product is prepared in the form of NaCl 0.9% plus B. subtilis and B. clausii at 1 billion CFU/mL x 30 mL.
• Probiotic 2
In Vietnam, LiveSpo Navax Kid is manufactured as a Class-A medical device (Product declaration: No. 220002534/PCBA-HN) in accordance with manufacturing standards approved by the Hanoi Health Department, Ministry of Health, Vietnam (Certificate No. YT117-19), and ISO 13485:2016. LiveSpo Navax Kid is prepared in the form of NaCl 0.9% plus B. subtilis and B. clausii at 0.6 billion CFU/mL x 30 mL.

Locations

Country	Name	City	State
Vietnam	Son Tay Province, Hanoi	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
Anabio R&D	Hanoi Medical University

Country where clinical trial is conducted

Vietnam, 

References & Publications (9)

Domachowske JB, Anderson EJ, Goldstein M. The Future of Respiratory Syncytial Virus Disease Prevention and Treatment. Infect Dis Ther. 2021 Mar;10(Suppl 1):47-60. doi: 10.1007/s40121-020-00383-6. Epub 2021 Mar 3. — View Citation

Greenwood B. The epidemiology of pneumococcal infection in children in the developing world. Philos Trans R Soc Lond B Biol Sci. 1999 Apr 29;354(1384):777-85. doi: 10.1098/rstb.1999.0430. — View Citation

Lee NK, Kim WS, Paik HD. Bacillus strains as human probiotics: characterization, safety, microbiome, and probiotic carrier. Food Sci Biotechnol. 2019 Oct 8;28(5):1297-1305. doi: 10.1007/s10068-019-00691-9. eCollection 2019 Oct. — View Citation

Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen M, McCracken GH Jr. Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics. 2004 Apr;113(4):701-7. doi: 10.1542/peds.113.4.701. — View Citation

Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, Matar C. Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders. Molecules. 2020 Oct 22;25(21):4891. doi: 10.3390/molecules25214891. — View Citation

Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, Alassani I, Ali A, Antonio M, Awasthi S, Awori JO, Azziz-Baumgartner E, Baggett HC, Baillie VL, Balmaseda A, Barahona A, Basnet S, Bassat Q, Basualdo W, Bigogo G, Bont L, Breiman RF, Brooks WA, Broor S, Bruce N, Bruden D, Buchy P, Campbell S, Carosone-Link P, Chadha M, Chipeta J, Chou M, Clara W, Cohen C, de Cuellar E, Dang DA, Dash-Yandag B, Deloria-Knoll M, Dherani M, Eap T, Ebruke BE, Echavarria M, de Freitas Lazaro Emediato CC, Fasce RA, Feikin DR, Feng L, Gentile A, Gordon A, Goswami D, Goyet S, Groome M, Halasa N, Hirve S, Homaira N, Howie SRC, Jara J, Jroundi I, Kartasasmita CB, Khuri-Bulos N, Kotloff KL, Krishnan A, Libster R, Lopez O, Lucero MG, Lucion F, Lupisan SP, Marcone DN, McCracken JP, Mejia M, Moisi JC, Montgomery JM, Moore DP, Moraleda C, Moyes J, Munywoki P, Mutyara K, Nicol MP, Nokes DJ, Nymadawa P, da Costa Oliveira MT, Oshitani H, Pandey N, Paranhos-Baccala G, Phillips LN, Picot VS, Rahman M, Rakoto-Andrianarivelo M, Rasmussen ZA, Rath BA, Robinson A, Romero C, Russomando G, Salimi V, Sawatwong P, Scheltema N, Schweiger B, Scott JAG, Seidenberg P, Shen K, Singleton R, Sotomayor V, Strand TA, Sutanto A, Sylla M, Tapia MD, Thamthitiwat S, Thomas ED, Tokarz R, Turner C, Venter M, Waicharoen S, Wang J, Watthanaworawit W, Yoshida LM, Yu H, Zar HJ, Campbell H, Nair H; RSV Global Epidemiology Network. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017 Sep 2;390(10098):946-958. doi: 10.1016/S0140-6736(17)30938-8. Epub 2017 Jul 7. — View Citation

Tiurin EA. [Effect of the use of dysentery divaccine as therapy in experimental radiation sickness on the immune response to heterologous antigens]. Radiobiologiia. 1982 May-Jun;22(3):395-8. No abstract available. Russian. — View Citation

Tran DM, Tran TT, Phung TTB, Bui HT, Nguyen PTT, Vu TT, Ngo NTP, Nguyen MT, Nguyen AH, Nguyen ATV. Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection. Sci Rep. 2022 Jul 20;12(1):12402. doi: 10.1038/s41598-022-16136-z. — View Citation

Tran TT, Phung TTB, Tran DM, Bui HT, Nguyen PTT, Vu TT, Ngo NTP, Nguyen MT, Nguyen AH, Nguyen ATV. Efficient symptomatic treatment and viral load reduction for children with influenza virus infection by nasal-spraying Bacillus spore probiotics. Sci Rep. 2023 Sep 8;13(1):14789. doi: 10.1038/s41598-023-41763-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of children with respiratory infections	Percentage (%) of children with respiratory infections (runny nose, stuffy nose, sneezing, sore throat, cough, feeling tired...) after 2 weeks and 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	The number of episodes of children with cold/illness/respiratory tract infections.	The number of episodes of children with cold/illness/respiratory tract infections after 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	Duration of illness	The average number of days per episode of cold/illness/respiratory tract infections at 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	Duration of school absence	The average number of days children have to be absent from school due to cold/illness/respiratory tract infections at 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	Duration of respiratory tract disease treatment	The average number of days children undergo treatment for each respiratory tract disease (bronchiolitis, pneumonia, pharyngitis, otitis media, asthma...) after 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	WURSS-K total score	The average total score of WURSS-K (Wisconsin Upper Respiratory Symptom Survey for Kids) evaluates children's respiratory infections when they are sick. WURSS-K is an instrument that measures illness-specific symptoms and their impact on the quality of life during upper respiratory tract infections (URTI). This tool includes 15 items: one global illness severity item (no. 1); six severity symptom-based items (no. 2-7); seven functional impact items (no. 8-14); one comparison item for assessing change over the days of an illness (no. 15).; Items from 1 to 14 are based on a 4-point ordinal Likert-type scale (0 = not sick/do not have this/not at all, 3 = very sick/very bad/very hard). The last item is based on a 5-point Likert-type scale. Happy and sad face representations are included along with the ordinal scales to facilitate survey completion by children.	2 weeks and 4 weeks
Secondary	Percentage (%) of children requiring medication treatment	Percentage (%) of children requiring medication treatments (antibiotics, anti-inflammatory, antipyretics, expectorants, infusion, bronchodilators...) after 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks
Secondary	The number of medication courses used in the treatment of respiratory tract diseases	The number of medication courses used for treating respiratory tract diseases with each type of medication (antibiotics, anti-inflammatory, antipyretics, expectorants, intravenous fluids, bronchodilators...) after 2 weeks and after 4 weeks of participating in the study.	2 weeks and 4 weeks
Secondary	Duration of treatment for respiratory tract diseases with each type of medication	The average number of days children undergo treatment with each type of medication (antibiotics, anti-inflammatory, antipyretics, expectorants, infusion, bronchodilators...) after 2 weeks and after 4 weeks of participating in the study	2 weeks and 4 weeks