URTIPhase 2NCT07498127
Effects of Probiotics on Respiratory Tract Infections in Children: A Randomized, Placebo-Controlled Interventional Study
A Phase 2 study testing Probiotic in people with URTI, run by Min-Tze LIONG at 2 sites in 2 countries.
Trial summary
This study is a 14-day, randomized, double-blind, placebo-controlled trial involving children aged 3 months to 6 years who meet clinical diagnostic criteria for mild to moderate upper respiratory tract infection (URTI). Read more about this study
- Who is it for?
- Ages 3 months to 6 years
- Conditions the study is for
- URTI
- What is being tested?
- Probiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Feb 2026to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged 3 months to 6 years, regardless of sex.
- Meet the clinical diagnostic criteria for upper respiratory tract infection, including but not limited to cough, rhinorrhea, nasal congestion, sore throat, and fever.
- Assessed by a clinician as having mild or moderate URTI, not requiring antibiotics or other systemic prescription medications, and suitable for observation and/or symptomatic management.
- Willing to discontinue other probiotics or supplements during the study period, except for the study product provided by the investigators.
- Agree to complete questionnaires and provide fecal biological samples during the study period.
- The child's parent(s) or legal guardian(s) are fully informed about the trial and voluntarily sign the written informed consent form before any study procedures begin.
Who cannot join
- Severe URTI as judged by the clinician, or symptoms severe enough to require antibiotics, corticosteroids, nebulized steroids/bronchodilators, or other systemic prescription medications, including suspected or confirmed bacterial infections such as bacterial tonsillitis, bacterial sinusitis, or acute suppurative otitis media.
- Acute lower respiratory tract infections, such as acute bronchitis, acute laryngitis/laryngospasm, or pneumonia.
- Respiratory tract infections secondary to underlying diseases, including primary immunodeficiency, acquired immunodeficiency syndrome, congenital airway malformation, congenital heart disease, gastroesophageal reflux, or abnormal lung development.
- Severe malnutrition.
- Severe chronic diseases, including severe asthma or other chronic respiratory diseases, chronic hepatitis or other liver diseases affecting liver function, renal insufficiency or other severe kidney diseases, neurological diseases such as epilepsy or neurodevelopmental disorders, and major genetic diseases such as chromosomal abnormalities or monogenic disorders.
- History of epilepsy or febrile convulsions.
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- Planned vaccination during the trial period.
- Severe infection, severe trauma, or history of medium-to-major surgery within the past month, as judged by the investigator.
- Participation in other clinical intervention studies involving drugs, dietary supplements, probiotics, or prebiotics within the past 3 months.
- Known allergy to any component of the probiotic product.
- Any other condition that, in the opinion of the investigator, makes the participant unsuitable for this clinical study.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
China1 site
Shanghai Sixth People's Hospital
Xuhui, Shanghai Municipality, 201306
About this study
This study is a 14-day, randomized, double-blind, placebo-controlled trial involving children aged 3 months to 6 years who meet clinical diagnostic criteria for mild to moderate upper respiratory tract infection (URTI). Participants are randomized to receive either a mixed probiotic preparation (Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V) or a placebo. The primary clinical outcome assessed is the duration and severity of respiratory symptoms. Secondary outcomes include changes in gut microbiota composition, intestinal immune markers, and quality of life. To investigate potential mechanisms, fecal samples are collected before and after intervention for metagenomic sequencing to analyze microbial diversity and composition, alongside immunological assessments such as sIgA and calprotectin.
Read the detailed description
Upper respiratory tract infection (URTI) is one of the most common pediatric illnesses, particularly affecting young children whose immune systems are still developing. Children under six years of age are especially susceptible to frequent infections, which can negatively impact growth, daily functioning, and overall quality of life. Although most URTIs are mild and self-limiting, recurrent or prolonged symptoms can lead to increased healthcare utilization, caregiver burden, and inappropriate antibiotic use, contributing to antimicrobial resistance. Therefore, safe and effective interventions that can reduce symptom severity and duration are of significant clinical importance.
The pathogenesis of URTI is multifactorial, involving viral exposure, host immune responses, and microbial ecosystem balance. Increasing evidence highlights the role of the gut-lung axis, a bidirectional communication pathway between the intestinal microbiota and the respiratory system. The gut microbiota plays a critical role in immune system maturation and regulation. Disruptions in microbial balance (dysbiosis) may impair immune defenses, making children more vulnerable to respiratory infections.
Probiotics, defined as live microorganisms that confer health benefits when administered in adequate amounts, have shown promise in modulating the gut microbiota and enhancing immune responses. Specific strains such as Lactobacillus rhamnosus and Bifidobacterium breve have been associated with improved mucosal immunity, including increased production of secretory immunoglobulin A (sIgA), regulation of inflammatory responses, and enhanced resistance to pathogens. These effects may translate into reduced severity and shorter duration of respiratory symptoms.
Several biological mechanisms have been proposed to explain how probiotics exert beneficial effects on respiratory health. The gastrointestinal and respiratory tracts are interconnected components of the mucosal immune system. Activation of gut-associated lymphoid tissue by probiotics can stimulate systemic immune responses, including the production of cytokines and immunoglobulins that enhance respiratory defense. Additionally, probiotics may influence metabolic pathways through the production of short-chain fatty acids, which have anti-inflammatory and immunomodulatory properties. Maintaining microbial balance in both the gut and respiratory tract is essential for optimal immune function.
Children with respiratory infections often exhibit reduced levels of beneficial gut bacteria, such as Lactobacillus and Bifidobacterium, along with altered immune markers. Probiotic supplementation may help restore this balance, improve intestinal barrier function, and enhance systemic immunity. Clinical benefits reported in previous studies include reduced symptom severity, faster recovery, and improved quality of life. Importantly, probiotics are generally well tolerated and have a strong safety profile in pediatric populations.
Based on this scientific rationale, the present study focuses on children aged 3 months to 6 years diagnosed with mild to moderate URTI. Participants will receive a fixed-dose combination of Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V (1 × 10¹⁰ CFU/day) or a placebo for 14 consecutive days. Clinical outcomes, including symptom duration and severity, will be evaluated alongside safety measures.
To further elucidate underlying mechanisms, fecal samples will be collected to assess gut microbiota composition using metagenomic sequencing, examining parameters such as alpha diversity, beta diversity, and relative abundance of key taxa. In addition, intestinal immune markers, including calprotectin (CALP) and secretory IgA (sIgA), will be measured. Quality of life will also be assessed using a pediatric respiratory questionnaire. Through the integration of clinical, microbiological, and immunological data, this study aims to clarify the therapeutic potential and mechanistic basis of probiotic intervention in pediatric URTI.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
Daily 6-drops of 1 × 10^10 CFU containing Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V in MCT oil
Placebo ControlDietary supplement
Daily 6-drops of MCT oil containing non-GMO corn starch
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Experimental | Daily 6-drops of 1 × 10^10 CFU containing Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V in MCT oil Receives: Dietary Supplement: Probiotic |
| Placebo | Placebo comparator | Daily 6-drops of MCT oil containing non-GMO cord starch Receives: Dietary Supplement: Placebo Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory symptoms in children upon administration of probiotic or placebo as assessed via clinical questionnaire
Differences in severity of respiratory symptoms in children upon administration of probiotic or placebo, assessed using a hospital-based clinical questionnaire scored on a 5-point ordinal scale (0 = no symptoms to 4 = severe symptoms), with lower scores indicating better respiratory status.
Measured: Day-0, Day-14
Secondary outcomes (3)
Quality of life in children upon administration of probiotic or placebo via clinical questionnaire
Differences in quality of life in children upon administration of probiotic or placebo, assessed using a hospital-based clinical questionnaire scored on a 5-point ordinal scale (4 = no symptoms to 0 = severe symptoms), with higher scores indicating better quality of life status.
Measured: Day-0, Day-14
Microbiota profiles of fecal samples in young children upon administration of probiotic or placebo as assessed via metagenomic sequencing
Differences in microbiota profiles in fecal sample of children upon administration of probiotic or placebo
Measured: Day-0, Day-14
Intestinal immune markers from fecal samples in young children upon administration of probiotic or placebo via use of Enzyme-Linked Immunosorbent Assay (ELISA)
Differences in intestinal immune markers profiles in fecal sample of children upon administration of probiotic or placebo, such as calprotectin and secretory immunoglobulin A (sIgA)
Measured: Day-0, Day-14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start1 Feb 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for URTIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Min-Tze LIONG
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai 6th People's Hospital
- Responsible party
- Sponsor-investigator, Min-Tze LIONG, Universiti Sains Malaysia
- Investigators
- Jinping Zhang, MD, Principal investigator, Shanghai 6th People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07498127
- Sponsor's protocol ID
- 2025-225-(1)
- Status last verified
- Mar 2026
- First submitted
- 23 Mar 2026
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Probiotics on Respiratory Tract Infections in Children: A Randomized, Placebo-Controlled Interventional Study
- ClinicalTrials.gov ID
- NCT07498127
- Acronym / sponsor ID
- 2025-225-(1)
- Conditions
- URTI
- Keywords
- URTI, probiotic, children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Min-Tze LIONGUniversity, hospital or other
- Collaborators
- Shanghai 6th People's Hospital
- Study start
- 1 Feb 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a 14-day, randomized, double-blind, placebo-controlled trial involving children aged 3 months to 6 years who meet clinical diagnostic criteria for mild to moderate upper respiratory tract infection (URTI). Participants are randomized to receive either a mixed probiotic preparation (Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V) or a placebo. The primary clinical outcome assessed is the duration and severity of respiratory symptoms. Secondary outcomes include changes in gut microbiota composition, intestinal immune markers, and quality of life. To investigate potential mechanisms, fecal samples are collected before and after intervention for metagenomic sequencing to analyze microbial diversity and composition, alongside immunological assessments such as sIgA and calprotectin.
Detailed description
Upper respiratory tract infection (URTI) is one of the most common pediatric illnesses, particularly affecting young children whose immune systems are still developing. Children under six years of age are especially susceptible to frequent infections, which can negatively impact growth, daily functioning, and overall quality of life. Although most URTIs are mild and self-limiting, recurrent or prolonged symptoms can lead to increased healthcare utilization, caregiver burden, and inappropriate antibiotic use, contributing to antimicrobial resistance. Therefore, safe and effective interventions that can reduce symptom severity and duration are of significant clinical importance.
The pathogenesis of URTI is multifactorial, involving viral exposure, host immune responses, and microbial ecosystem balance. Increasing evidence highlights the role of the gut-lung axis, a bidirectional communication pathway between the intestinal microbiota and the respiratory system. The gut microbiota plays a critical role in immune system maturation and regulation. Disruptions in microbial balance (dysbiosis) may impair immune defenses, making children more vulnerable to respiratory infections.
Probiotics, defined as live microorganisms that confer health benefits when administered in adequate amounts, have shown promise in modulating the gut microbiota and enhancing immune responses. Specific strains such as Lactobacillus rhamnosus and Bifidobacterium breve have been associated with improved mucosal immunity, including increased production of secretory immunoglobulin A (sIgA), regulation of inflammatory responses, and enhanced resistance to pathogens. These effects may translate into reduced severity and shorter duration of respiratory symptoms.
Several biological mechanisms have been proposed to explain how probiotics exert beneficial effects on respiratory health. The gastrointestinal and respiratory tracts are interconnected components of the mucosal immune system. Activation of gut-associated lymphoid tissue by probiotics can stimulate systemic immune responses, including the production of cytokines and immunoglobulins that enhance respiratory defense. Additionally, probiotics may influence metabolic pathways through the production of short-chain fatty acids, which have anti-inflammatory and immunomodulatory properties. Maintaining microbial balance in both the gut and respiratory tract is essential for optimal immune function.
Children with respiratory infections often exhibit reduced levels of beneficial gut bacteria, such as Lactobacillus and Bifidobacterium, along with altered immune markers. Probiotic supplementation may help restore this balance, improve intestinal barrier function, and enhance systemic immunity. Clinical benefits reported in previous studies include reduced symptom severity, faster recovery, and improved quality of life. Importantly, probiotics are generally well tolerated and have a strong safety profile in pediatric populations.
Based on this scientific rationale, the present study focuses on children aged 3 months to 6 years diagnosed with mild to moderate URTI. Participants will receive a fixed-dose combination of Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V (1 × 10¹⁰ CFU/day) or a placebo for 14 consecutive days. Clinical outcomes, including symptom duration and severity, will be evaluated alongside safety measures.
To further elucidate underlying mechanisms, fecal samples will be collected to assess gut microbiota composition using metagenomic sequencing, examining parameters such as alpha diversity, beta diversity, and relative abundance of key taxa. In addition, intestinal immune markers, including calprotectin (CALP) and secretory IgA (sIgA), will be measured. Quality of life will also be assessed using a pediatric respiratory questionnaire. Through the integration of clinical, microbiological, and immunological data, this study aims to clarify the therapeutic potential and mechanistic basis of probiotic intervention in pediatric URTI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Experimental | Dietary Supplement: ProbioticDaily 6-drops of 1 × 10^10 CFU containing Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V in MCT oil |
| Placebo | Placebo comparator | Dietary Supplement: Placebo ControlDaily 6-drops of MCT oil containing non-GMO cord starch |
Who may qualify
- Ages
- 3 months to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Children aged 3 months to 6 years, regardless of sex.
- Meet the clinical diagnostic criteria for upper respiratory tract infection, including but not limited to cough, rhinorrhea, nasal congestion, sore throat, and fever.
- Assessed by a clinician as having mild or moderate URTI, not requiring antibiotics or other systemic prescription medications, and suitable for observation and/or symptomatic management.
- Willing to discontinue other probiotics or supplements during the study period, except for the study product provided by the investigators.
- Agree to complete questionnaires and provide fecal biological samples during the study period.
Key exclusion criteria (11 listed)
- Severe URTI as judged by the clinician, or symptoms severe enough to require antibiotics, corticosteroids, nebulized steroids/bronchodilators, or other systemic prescription medications, including suspected or confirmed bacterial infections such as bacterial tonsillitis, bacterial sinusitis, or acute suppurative otitis media.
- Acute lower respiratory tract infections, such as acute bronchitis, acute laryngitis/laryngospasm, or pneumonia.
- Respiratory tract infections secondary to underlying diseases, including primary immunodeficiency, acquired immunodeficiency syndrome, congenital airway malformation, congenital heart disease, gastroesophageal reflux, or abnormal lung development.
- Severe malnutrition.
- Severe chronic diseases, including severe asthma or other chronic respiratory diseases, chronic hepatitis or other liver diseases affecting liver function, renal insufficiency or other severe kidney diseases, neurological diseases such as epilepsy or neurodevelopmental disorders, and major genetic diseases such as chromosomal abnormalities or monogenic disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticDaily 6-drops of 1 × 10^10 CFU containing Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V in MCT oil | Dietary supplement | Probiotic |
| Placebo ControlDaily 6-drops of MCT oil containing non-GMO corn starch | Dietary supplement | Placebo |
Primary outcome
Respiratory symptoms in children upon administration of probiotic or placebo as assessed via clinical questionnaire
Time frame: Day-0, Day-14
Differences in severity of respiratory symptoms in children upon administration of probiotic or placebo, assessed using a hospital-based clinical questionnaire scored on a 5-point ordinal scale (0 = no symptoms to 4 = severe symptoms), with lower scores indicating better respiratory status.
3 secondary outcomes
Quality of life in children upon administration of probiotic or placebo via clinical questionnaire
Time frame: Day-0, Day-14
Microbiota profiles of fecal samples in young children upon administration of probiotic or placebo as assessed via metagenomic sequencing
Time frame: Day-0, Day-14
Intestinal immune markers from fecal samples in young children upon administration of probiotic or placebo via use of Enzyme-Linked Immunosorbent Assay (ELISA)
Time frame: Day-0, Day-14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jinping Zhang, MD principal investigator
Shanghai 6th People's Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Probiotic in people with URTI, run by Min-Tze LIONG at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory symptoms in children upon administration of probiotic or placebo as assessed via clinical questionnaire (time frame: Day-0, Day-14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.