Recurrent Respiratory Tract InfectionsLR_D3NCT04408443
Evaluation of Lactobacillus Reuteri DSM 17938 + Vitamin D3 in the Prevention of RRI in Paediatric Patients
A study testing Lactobacillus reuteri DSM 17938 + Vitamine D3 in people with Recurrent Respiratory Tract Infections, run by Noos S.r.l. at 1 site in Italy.
Trial summary
The aim of this protocol is to evaluate, in a multicenter, randomized, double blind vs placebo clinical trial the effects of a marketed food supplement containing Lactobacillus reuteri DSM 17938 and vitamin D3 (Reuterin® D3) in the prevention of recurrent respiratory infections in pediatric patients suffered from… Read more about this study
- Who is it for?
- Ages 1 year to 6 yearsHealthy volunteers can take part
- Conditions the study is for
- Recurrent Respiratory Tract Infections
- What is being tested?
- Lactobacillus reuteri DSM 17938 + Vitamine D3
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 25 Nov 2019to 30 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 1 year to 6 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Patients between 1 and 6 years of age at the enrollment; both sexes
- Patients with an history of RRI, according to the definition (The definition of Recurrent respiratory infections (RRI) is the onset of 8 or more documented airway infections during the year, in preschool children (up to three years of age) or 6 or more in children older 3 years, in the absence of any other underlying pathological condition) in the previous year.
- Atopic and non-atopic patients
- Willing and able to give informed consent of participation in the study by parent or legal guardian.
Who cannot join
- Presence of autoimmune diseases, immunodeficiency, neuromuscular diseases, congenital cardiomyopathies, metabolic diseases
- Patients in therapy with other drugs for the treatment of RRI
- Supplementation with probiotics and /or prebiotics in the previous 2 weeks
- Vitamin D intake in the last 4 weeks
- IgA deficiency
- Antibiotic treatment at least 4 week before in inclusion
- Participation in other clinical trials
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of a Food Supplement Containing Lactobacillus Reuteri DSM 17938 + Vitamin D3 in the Prevention of Recurrent Respiratory Infections in Paediatric Patients
The aim of this protocol is to evaluate, in a multicenter, randomized, double blind vs placebo clinical trial the effects of a marketed food supplement containing Lactobacillus reuteri DSM 17938 and vitamin D3 (Reuterin® D3) in the prevention of recurrent respiratory infections in pediatric patients suffered from Recurrent Respiratory Infection (RRI) in previous years.
Read the detailed description
Several clinical trials documented the efficacy of probiotics in the prevention and treatment of acute gastroenteritis, while there is little evidence on the efficacy of the probiotics in the prevention of children respiratory infections.
The biological activity of probiotics is linked, partly, to their capacity to adhere to enterocytes. This would avoid the binding of pathogenic bacteria through a competitive exclusion mechanism. This inhibition toward pathogen bacteria on epithelial and mucosal level (substrate), thanks also to the production of antimicrobial substances, can have a beneficial effect on the balance of the intestinal microflora of the host and improve its immunity.
The adhesion of probiotic bacteria to the enterocyte membrane receptors influences the activation of second messengers that induces the production of cytokines. The presence of probiotic bacteria influences the commensal microorganisms in the production of lactic acid and bacteriocins. These substances inhibit the growth of pathogens and modify the balance of commensal bacteria of the intestinal bacterial flora.
Numerous controlled clinical trials show that L. reuteri DSM 17938 colonizes the human gastric and intestinal epithelium and modulates the immune response, particularly through CD4 + T-helper cells in the ileum. These data confirm the pre-clinical evidence obtained in animal models; furthermore these immunomodulatory effects may explain some clinical properties of L. reuteri DSM 17938 such as the prevention of diarrhea, inhibition of pathogen infectionand the following immune system response of the host to these pathogens, as well as the potential modulation of the immune response by the Th1/Th2 balance in the human intestinal epithelium, an answer that has been linked to the prevention and treatment of allergy. In a recent, randomized, double-blind, placebo-controlled clinical trial, L. reuteri DSM 17938, supplemented for three months to healthy children aged 6-36 months attending nursery schools, demonstrated not only a significant reduction of episodes and duration of diarrhea but also of respiratory tract infections with consequent reduction of costs for society.
Despite the prevalence of food with vitamin D and multivitamin products, reports regarding non-optimal vitamin D levels in adults and children in the world have increased, in particular among those subjects overweight and with dark pigmentation of the skin.
In addition to its well-known effects on bone health, vitamin D is indeed an important immune regulator, because it stimulates innate immunity and modulates inflammation. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) between 1988 and 1994 showed an inverse relationship between vitamin D levels and the incidence of upper respiratory tract infections (URTI). These results were supported by other studies showing an increased risk of acute lower respiratory tract infections in subjects with low levels of vitamin D.
Historically, the association between rickets and the risk of serious respiratory infections is well known and vitamin D deficiency has been associated with an increased risk to contract the flu.
These considerations have led to the hypothesis that supplementation with a probiotic added with vitamin D3 may influence the composition of intestinal flora by improving the immune system and therefore reducing episodes of respiratory infections, particularly frequent during preschool age.
- Conditions
- Recurrent Respiratory Tract Infections
- Being tested
- Lactobacillus reuteri DSM 17938 + Vitamine D3, Placebo
- Keywords
- RRI, probiotics, vitamin D3, L. reuteri
- Medical subject headings
- Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus reuteri DSM 17938 + Vitamine D3Dietary supplement
Lactobacillus reuteri DSM 17938 (10E8 CFU in 5 drops), Vitamin D3 (400 IU in 5 drops), sunflower oil, medium chain triglycerides, silicon dioxide
PlaceboDietary supplement
sunflower oil, medium chain triglycerides, silicon dioxide
| Study group | Role | What they receive |
|---|---|---|
| Reuterin D3 | Active comparator | Patients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up. Receives: Dietary Supplement: Lactobacillus reuteri DSM 17938 + Vitamine D3 |
| Placebo | Placebo comparator | Patients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of the number of respiratory infection
Change of the number of respiratory infection respect the previous year
Measured: 4 months + 2 months of follow up
Secondary outcomes (6)
Change of number of days with fever
To evaluate the change of the number of days with fever
Measured: 4 months + 2 months of follow up
Change of the antibiotic use
To evaluate the change of the antibiotic use
Measured: 4 months + 2 months of follow up
Change of number of visit to Pediatrician
To evaluate the change of the number of visit to Pediatrician
Measured: 4 months + 2 months of follow up
Change of number of days of absence from the nursery / kindergarten
To evaluate the change of the number of days of absence from the nursery / kindergarten
Measured: 4 months + 2 months of follow up
Changes of days of absence from work by parents
To evaluate the change of days of absence from work by parents
Measured: 4 months + 2 months of follow up
Modification of intestinal microflora
To evaluate the modification of intestinal microflora
Measured: 4 months + 2 months of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2020
- Study start25 Nov 2019
- Primary completion30 Sep 2021
- Study completion30 Sep 2021
Why it stopped: No enrollment due COVID PANDEMIA
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Respiratory Tract InfectionsStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noos S.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michele Miraglia del Giudice, Prof., Principal investigator, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04408443
- Sponsor's protocol ID
- IRR_D3
- Acronym
- LR_D3
- Status last verified
- Mar 2023
- First submitted
- 25 May 2020
- Last updated
- 23 Mar 2023
- 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 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Food Supplement Containing Lactobacillus Reuteri DSM 17938 + Vitamin D3 in the Prevention of Recurrent Respiratory Infections in Paediatric Patients
- ClinicalTrials.gov ID
- NCT04408443
- Acronym / sponsor ID
- LR_D3 / IRR_D3
- Conditions
- Recurrent Respiratory Tract Infections
- Keywords
- RRI, probiotics, vitamin D3, L. reuteri
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No enrollment due COVID PANDEMIA
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Noos S.r.l.Industry (pharma, biotech, devices)
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 29 May 2020 (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.
The aim of this protocol is to evaluate, in a multicenter, randomized, double blind vs placebo clinical trial the effects of a marketed food supplement containing Lactobacillus reuteri DSM 17938 and vitamin D3 (Reuterin® D3) in the prevention of recurrent respiratory infections in pediatric patients suffered from Recurrent Respiratory Infection (RRI) in previous years.
Detailed description
Several clinical trials documented the efficacy of probiotics in the prevention and treatment of acute gastroenteritis, while there is little evidence on the efficacy of the probiotics in the prevention of children respiratory infections.
The biological activity of probiotics is linked, partly, to their capacity to adhere to enterocytes. This would avoid the binding of pathogenic bacteria through a competitive exclusion mechanism. This inhibition toward pathogen bacteria on epithelial and mucosal level (substrate), thanks also to the production of antimicrobial substances, can have a beneficial effect on the balance of the intestinal microflora of the host and improve its immunity.
The adhesion of probiotic bacteria to the enterocyte membrane receptors influences the activation of second messengers that induces the production of cytokines. The presence of probiotic bacteria influences the commensal microorganisms in the production of lactic acid and bacteriocins. These substances inhibit the growth of pathogens and modify the balance of commensal bacteria of the intestinal bacterial flora.
Numerous controlled clinical trials show that L. reuteri DSM 17938 colonizes the human gastric and intestinal epithelium and modulates the immune response, particularly through CD4 + T-helper cells in the ileum. These data confirm the pre-clinical evidence obtained in animal models; furthermore these immunomodulatory effects may explain some clinical properties of L. reuteri DSM 17938 such as the prevention of diarrhea, inhibition of pathogen infectionand the following immune system response of the host to these pathogens, as well as the potential modulation of the immune response by the Th1/Th2 balance in the human intestinal epithelium, an answer that has been linked to the prevention and treatment of allergy. In a recent, randomized, double-blind, placebo-controlled clinical trial, L. reuteri DSM 17938, supplemented for three months to healthy children aged 6-36 months attending nursery schools, demonstrated not only a significant reduction of episodes and duration of diarrhea but also of respiratory tract infections with consequent reduction of costs for society.
Despite the prevalence of food with vitamin D and multivitamin products, reports regarding non-optimal vitamin D levels in adults and children in the world have increased, in particular among those subjects overweight and with dark pigmentation of the skin.
In addition to its well-known effects on bone health, vitamin D is indeed an important immune regulator, because it stimulates innate immunity and modulates inflammation. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) between 1988 and 1994 showed an inverse relationship between vitamin D levels and the incidence of upper respiratory tract infections (URTI). These results were supported by other studies showing an increased risk of acute lower respiratory tract infections in subjects with low levels of vitamin D.
Historically, the association between rickets and the risk of serious respiratory infections is well known and vitamin D deficiency has been associated with an increased risk to contract the flu.
These considerations have led to the hypothesis that supplementation with a probiotic added with vitamin D3 may influence the composition of intestinal flora by improving the immune system and therefore reducing episodes of respiratory infections, particularly frequent during preschool age.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reuterin D3 | Active comparator | Dietary Supplement: Lactobacillus reuteri DSM 17938 + Vitamine D3Patients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPatients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up. |
Who may qualify
- Ages
- 1 year to 6 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Patients between 1 and 6 years of age at the enrollment; both sexes
- Patients with an history of RRI, according to the definition (The definition of Recurrent respiratory infections (RRI) is the onset of 8 or more documented airway infections during the year, in preschool children (up to three years of age) or 6 or more in children older 3 years, in the absence of any other underlying pathological condition) in the previous year.
- Atopic and non-atopic patients
- Willing and able to give informed consent of participation in the study by parent or legal guardian.
Key exclusion criteria (7 listed)
- Presence of autoimmune diseases, immunodeficiency, neuromuscular diseases, congenital cardiomyopathies, metabolic diseases
- Patients in therapy with other drugs for the treatment of RRI
- Supplementation with probiotics and /or prebiotics in the previous 2 weeks
- Vitamin D intake in the last 4 weeks
- IgA deficiency
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 |
|---|---|---|
| Lactobacillus reuteri DSM 17938 + Vitamine D3Lactobacillus reuteri DSM 17938 (10E8 CFU in 5 drops), Vitamin D3 (400 IU in 5 drops), sunflower oil, medium chain triglycerides, silicon dioxide | Dietary supplement | Reuterin D3 |
| Placebosunflower oil, medium chain triglycerides, silicon dioxide | Dietary supplement | Placebo |
Primary outcome
Change of the number of respiratory infection
Time frame: 4 months + 2 months of follow up
Change of the number of respiratory infection respect the previous year
6 secondary outcomes
Change of number of days with fever
Time frame: 4 months + 2 months of follow up
Change of the antibiotic use
Time frame: 4 months + 2 months of follow up
Change of number of visit to Pediatrician
Time frame: 4 months + 2 months of follow up
Change of number of days of absence from the nursery / kindergarten
Time frame: 4 months + 2 months of follow up
Changes of days of absence from work by parents
Time frame: 4 months + 2 months of follow up
Modification of intestinal microflora
Time frame: 4 months + 2 months of follow up
Results and safety
The study was stopped early (reason given: No enrollment due COVID PANDEMIA). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
- 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. This study is not recruiting at the moment.
Michele Miraglia del Giudice, Prof. principal investigator
University of Campania Luigi Vanvitelli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus reuteri DSM 17938 + Vitamine D3 in people with Recurrent Respiratory Tract Infections, run by Noos S.r.l. at 1 site in Italy.
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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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.
Are results available for this study?
The study was stopped early (reason given: No enrollment due COVID PANDEMIA). Results are not available in the source record.
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?
Change of the number of respiratory infection (time frame: 4 months + 2 months of follow up). 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 23 Mar 2023.