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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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.

Italy1 site
  • University of Campania Luigi Vanvitelli

    Naples, 80138

Other trials in Italy

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.

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 groups in NCT04408443
Study groupRoleWhat they receive
Reuterin D3Active comparatorPatients 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
PlaceboPlacebo comparatorPatients 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.

  1. 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)
  1. 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

  2. Change of the antibiotic use

    To evaluate the change of the antibiotic use

    Measured: 4 months + 2 months of follow up

  3. 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

  4. 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

  5. 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

  6. 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.

  1. First posted29 May 2020
  2. Study start25 Nov 2019
  3. Primary completion30 Sep 2021
  4. Study completion30 Sep 2021

Why it stopped: No enrollment due COVID PANDEMIA

Resources

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)
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

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.

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