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TerminatedNCT04408443LR_D3Updated Mar 23, 2023

Evaluation of Lactobacillus Reuteri DSM 17938 + Vitamin D3 in the Prevention of RRI in Paediatric Patients

An interventional study of Lactobacillus reuteri DSM 17938 + Vitamine D3 and Placebo in Recurrent Respiratory Tract Infections, sponsored by Noos S.r.l.. Terminated at 1 site in Italy. Open to participants aged 1 Year to 6 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-03-23.

Sponsored by Noos S.r.l. · Not applicable, Interventional, and Prevention

Why this study was terminated
No enrollment due COVID PANDEMIA

From the registry’s dates

  • Registered 6 months after the study started (first participant enrolled Nov 2019, registered May 2020).
Phase
Not applicable
Study type
Interventional
Enrollment
200
Allocation
Randomized
Ages
1 Year to 6 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • Recurrent Respiratory Tract Infections

Keywords

  • RRI, probiotics, vitamin D3, L. reuteri
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 200 is above the median of 120 across 4,201 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

Noos S.r.l. is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Year to 6 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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
05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
200 participants (actual)

Study arms

  • Active comparator
    Reuterin D3

    Patients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up.

    Dietary Supplement: Lactobacillus reuteri DSM 17938 + Vitamine D3

  • Placebo comparator
    Placebo

    Patients should take 10 drops once a day during meals for 4 months followed by 2 months of follow up.

    Dietary Supplement: Placebo

Interventions

  • Dietary supplementLactobacillus reuteri DSM 17938 + Vitamine D3

    Lactobacillus reuteri DSM 17938 (10E8 CFU in 5 drops), Vitamin D3 (400 IU in 5 drops), sunflower oil, medium chain triglycerides, silicon dioxide

  • Dietary supplementPlacebo

    sunflower oil, medium chain triglycerides, silicon dioxide

06

What researchers measure

Primary outcomes

  1. Change of the number of respiratory infection

    Change of the number of respiratory infection respect the previous year

    Time frame: 4 months + 2 months of follow up

Secondary outcomes

  1. Change of number of days with fever

    To evaluate the change of the number of days with fever

    Time frame: 4 months + 2 months of follow up

  2. Change of the antibiotic use

    To evaluate the change of the antibiotic use

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 4 months + 2 months of follow up

  6. Modification of intestinal microflora

    To evaluate the modification of intestinal microflora

    Time frame: 4 months + 2 months of follow up

07

Study locations

1 site
  • University of Campania Luigi Vanvitelli
    Naples, 80138, Italy
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 23, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04408443
Lead sponsor
Noos S.r.l.
Responsible party
Sponsor
First posted
May 29, 2020
Start date
Nov 25, 2019
Primary completion
Sep 30, 2021
Completion
Sep 30, 2021
Last update
Mar 23, 2023

Study contacts

Michele Miraglia del Giudice, Prof.
principal investigator · University of Campania Luigi Vanvitelli

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.

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