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Efficacy and Safety of L. Plantarum and P. Acidilactici in Children With Upper Respiratory Tract Infections

Primary Purpose

Upper Respiratory Tract Infections, Pharyngitis, Tonsillitis

Status
Terminated
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Probiotic
Placebo
Sponsored by
AB Biotics, SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Upper Respiratory Tract Infections focused on measuring Probiotic

Eligibility Criteria

6 Months - 5 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female children, 6 months to 5 years-old
  • Diagnosed with upper respiratory tract infection with pharyngitis and/or tonsillitis by a physician
  • With fever >37.5 Celsius degrees and FLACC (Face, Legs, Activity, Cry and Consolability) score >3
  • Symptom onset no more than 48h before study entry
  • Body weight at birth >2500 gr
  • Informed consent provided by parents or legal guardians

Exclusion Criteria:

  • Failure to thrive
  • Asthma or significant allergic disease
  • Use of antibiotics, antivirals, probiotics or prebiotics for more than 48h within 2 weeks of study entry
  • History of recurrent respiratory infections (>2 otitis, >1 severe sinusitis or >1 pneumonia) within 12 months of study entry
  • History of 2 or more invasive infections (meningitis, cellulitis, osteomyelitis, sepsis)
  • Chronic diarrhea or short bowel syndrome
  • Congenital heart or respiratory deficiency
  • Known alpha1-antitrypsin deficiency
  • Concurrent participation in other clinical trial(s)
  • Other particular conditions which, in the judgment of the Principal Investigator, may interfere with the study

Sites / Locations

  • Hospital General Dr. Manuel Gea Gonzalez

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Probiotic

Control

Arm Description

Active test product contains four lactic acid bacteria strains with Qualified Presumption of Safety (QPS) status by European Food Safety Authority (EFSA): Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, with maltodextrin (E1400, qs) as excipient, formulated in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0. Active test product is a food supplement and not an investigational medicinal product

The control study product is identical in packaging and formulation except that none of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485 and Pediococcus acidilactici CECT7483 (probiotic bacteria) are present. The Control product contains maltodextrin (E1400, qs) only, in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0.

Outcomes

Primary Outcome Measures

Daily evolution of fever
Daily severity of fever (Celsius degrees), as measured with an infrared thermometer (same model for all recruited subjects) and noted in patient diary
Daily evolution of pain
Daily severity of pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) and noted in patient diary

Secondary Outcome Measures

Fever Area Under the Curve
Area Under the Curve (AUC) of daily fever (body temperature, Celsius degrees)
Pain Area Under the Curve
Area Under the Curve (AUC) of daily pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain])
Days with fever
Days with body temperature > 37.5 Celsius, as noted in patient diary
Days with pain
Days with pain as per FLACC scale (Face, Legs, Activity, Cry and Consolability), as noted in patient diary
Days with rhinorrhea
Days with runny nose, as noted in patient diary
Days with cough
Days of cough, as noted in patient diary
Days with nasal congestion
Days of nasal congestion, as noted in patient diary
Days with any symptom
Days with one or more of the following symptom: fever, pain, rhinorrhea, cough or nasal congestion (as noted in patient diary)
Days with concomitant medication
Days of intake of NSAIDS (non-steroidal anti-inflammatory drugs) and/or antihistamines, as noted in patient diary
Number of children receiving antibiotics
Number of children receiving antibiotics
Number of hospitalizations
Number of children being hospitalized related to respiratory tract infection
Number of medical or emergency visits
Number of medical or emergency visits related to respiratory tract infection
Days of schooling absence
Days of daycare or kindergarten absence, as noted in patient diary
Change in salivary immune biomarkers
Change in concentration of Immunoglobulin A (IgA), Tumor Necrosis Factor-alpha (TNFa), Interleukin 1-beta (IL-1b) and Interleukin 10 (IL-10) in saliva samples
Total treatment costs
Cost of medical and emergency visits, drug treatments (anti-inflammatory drugs, anti-histamines and antibiotics) and schooling absence
Time to fever resolution
Time to body temperature at or below 37.5 Celsius, as noted in patient diary
Time to pain resolution
Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) score < 2, as noted in patient diary
Time to complete symptom resolution
Time to clearance of all of the following symptoms: fever, pain, rhinorrhea, cough and nasal congestion, as noted in patient diary
Time to fever recurrence
Time to body temperature >37.5 Celsius after initial resolution (see outcome #19), as noted in patient diary
Time to pain recurrence
Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) score > 3 after initial resolution (see outcome #20), as noted in patient diary
Time to any symptom recurrence
Time to recurrence of any symptom (fever, pain, rhinorrhea, cough and nasal congestion) after initial complete symptom resolution (see outcome #21), as noted in patient diary
Change in microbiota
Change in microbiota composition, as determined by 16S gene sequencing

Full Information

First Posted
March 7, 2022
Last Updated
October 16, 2023
Sponsor
AB Biotics, SA
Collaborators
Innovacion y Desarrollo de Estrategias en Salud, Hospital General Dr. Manuel Gea González
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1. Study Identification

Unique Protocol Identification Number
NCT05279534
Brief Title
Efficacy and Safety of L. Plantarum and P. Acidilactici in Children With Upper Respiratory Tract Infections
Official Title
Efficacy and Safety of Lactobacillus Plantarum and Pediococcus Acidilactici as Twice-daily Co-adjuvant Therapy of Upper Respiratory Tract Infections in Children 6 Months to 5 Years Old
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
March 8, 2022 (Actual)
Primary Completion Date
June 2, 2023 (Actual)
Study Completion Date
June 2, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Biotics, SA
Collaborators
Innovacion y Desarrollo de Estrategias en Salud, Hospital General Dr. Manuel Gea González

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Randomized, placebo-controlled trial to evaluate the coadjuvant effect of a combination of L. plantarum and P. acidilactici probiotic strains, taken twice daily, in children 6 months to 5 years-old with upper respiratory tract infections with pharyngitis and/or tonsillitis. Main objective is to evaluate efficacy of this probiotic in reducing fever and pain, as well to evaluate its safety.
Detailed Description
Randomized, placebo-controlled trial (RCT) to evaluate the coadjuvant effect of probiotic strains L. plantarum CECT30292, L.plantarum CECT7484 and CECT7485 together with P. acidilactici CECT7483, taken twice daily, in children 6 months to 5 years-old with upper respiratory tract infections with pharyngitis and/or tonsillitis, as diagnosed by a physician. Main objective is to evaluate efficacy of this probiotic in reducing fever (as per infrared thermometer, same model for all recruited subjects) and pain (as per FLACC scale [Face, Legs, Activity, Cry and Consolability]), as well to evaluate its safety. Secondary objectives include effect on cough, rhinorrhea, nasal congestion, use of concomitant medication, emergency visits, hospitalizations, schooling absences and salivary immune markers. Probiotic intervention will last 15 days, and patients will return for follow-up visits on the last day of probiotic intervention (day 15), and well as day 30 and 60. The study aims at enrolling and randomizing 80 children fulfilling entry criteria and living in Mexico City area (2,200m over the sea level), after parents or legal guardians sign informed consent.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Upper Respiratory Tract Infections, Pharyngitis, Tonsillitis
Keywords
Probiotic

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled trials. Study subjects (6 months to 5 years-old) will be allocated to receive a combination of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and P. acidilactici CECT7483 (arm one) or placebo (arm two)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All study staff, including the Principal Investigator and the persons performing the subject assessments, will be blinded during the study. Sealed individual treatment code envelopes will be kept at the clinic to be able to break the code if any emergency occurs, as judged by the Investigator
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Probiotic
Arm Type
Experimental
Arm Description
Active test product contains four lactic acid bacteria strains with Qualified Presumption of Safety (QPS) status by European Food Safety Authority (EFSA): Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, with maltodextrin (E1400, qs) as excipient, formulated in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0. Active test product is a food supplement and not an investigational medicinal product
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
The control study product is identical in packaging and formulation except that none of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485 and Pediococcus acidilactici CECT7483 (probiotic bacteria) are present. The Control product contains maltodextrin (E1400, qs) only, in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0.
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotic
Intervention Description
Combination of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, twice daily for 15 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Combination of maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0, twice daily for 15 days
Primary Outcome Measure Information:
Title
Daily evolution of fever
Description
Daily severity of fever (Celsius degrees), as measured with an infrared thermometer (same model for all recruited subjects) and noted in patient diary
Time Frame
Day 1 to 15
Title
Daily evolution of pain
Description
Daily severity of pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) and noted in patient diary
Time Frame
Day 1 to 15
Secondary Outcome Measure Information:
Title
Fever Area Under the Curve
Description
Area Under the Curve (AUC) of daily fever (body temperature, Celsius degrees)
Time Frame
Day 1 to 60
Title
Pain Area Under the Curve
Description
Area Under the Curve (AUC) of daily pain, as per FLACC scale (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain])
Time Frame
Day 1 to 60
Title
Days with fever
Description
Days with body temperature > 37.5 Celsius, as noted in patient diary
Time Frame
Day 1 to 60
Title
Days with pain
Description
Days with pain as per FLACC scale (Face, Legs, Activity, Cry and Consolability), as noted in patient diary
Time Frame
Day 1 to 60
Title
Days with rhinorrhea
Description
Days with runny nose, as noted in patient diary
Time Frame
Day 1 to 60
Title
Days with cough
Description
Days of cough, as noted in patient diary
Time Frame
Day 1 to 60
Title
Days with nasal congestion
Description
Days of nasal congestion, as noted in patient diary
Time Frame
Day 1 to 60
Title
Days with any symptom
Description
Days with one or more of the following symptom: fever, pain, rhinorrhea, cough or nasal congestion (as noted in patient diary)
Time Frame
Day 1 to 60
Title
Days with concomitant medication
Description
Days of intake of NSAIDS (non-steroidal anti-inflammatory drugs) and/or antihistamines, as noted in patient diary
Time Frame
Day 1 to 60
Title
Number of children receiving antibiotics
Description
Number of children receiving antibiotics
Time Frame
Day 1 to 60
Title
Number of hospitalizations
Description
Number of children being hospitalized related to respiratory tract infection
Time Frame
Day 1 to 60
Title
Number of medical or emergency visits
Description
Number of medical or emergency visits related to respiratory tract infection
Time Frame
Day 1 to 60
Title
Days of schooling absence
Description
Days of daycare or kindergarten absence, as noted in patient diary
Time Frame
Day 1 to 60
Title
Change in salivary immune biomarkers
Description
Change in concentration of Immunoglobulin A (IgA), Tumor Necrosis Factor-alpha (TNFa), Interleukin 1-beta (IL-1b) and Interleukin 10 (IL-10) in saliva samples
Time Frame
Day 1 to 15
Title
Total treatment costs
Description
Cost of medical and emergency visits, drug treatments (anti-inflammatory drugs, anti-histamines and antibiotics) and schooling absence
Time Frame
Day 1 to 60
Title
Time to fever resolution
Description
Time to body temperature at or below 37.5 Celsius, as noted in patient diary
Time Frame
Day 1 to 15
Title
Time to pain resolution
Description
Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) score < 2, as noted in patient diary
Time Frame
Day 1 to 15
Title
Time to complete symptom resolution
Description
Time to clearance of all of the following symptoms: fever, pain, rhinorrhea, cough and nasal congestion, as noted in patient diary
Time Frame
Day 1 to 15
Title
Time to fever recurrence
Description
Time to body temperature >37.5 Celsius after initial resolution (see outcome #19), as noted in patient diary
Time Frame
Day 15 to 60
Title
Time to pain recurrence
Description
Time to FLACC (Face, Legs, Activity, Cry and Consolability, ranging 0 [no pain] to 10 [maximum pain]) score > 3 after initial resolution (see outcome #20), as noted in patient diary
Time Frame
Day 15 to 60
Title
Time to any symptom recurrence
Description
Time to recurrence of any symptom (fever, pain, rhinorrhea, cough and nasal congestion) after initial complete symptom resolution (see outcome #21), as noted in patient diary
Time Frame
Day 15 to 60
Title
Change in microbiota
Description
Change in microbiota composition, as determined by 16S gene sequencing
Time Frame
Day 1 to 15
Other Pre-specified Outcome Measures:
Title
Etiology of the upper respiratory tract infection at baseline
Description
Identification of the viral or bacterial pathogen responsible for the baseline episode of upper respiratory tract infection by molecular methods
Time Frame
Day 1
Title
Salivary vitamin D at baseline
Description
Concentration of vitamin D at baseline as measured in saliva sample
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female children, 6 months to 5 years-old Diagnosed with upper respiratory tract infection with pharyngitis and/or tonsillitis by a physician With fever >37.5 Celsius degrees and FLACC (Face, Legs, Activity, Cry and Consolability) score >3 Symptom onset no more than 48h before study entry Body weight at birth >2500 gr Informed consent provided by parents or legal guardians Exclusion Criteria: Failure to thrive Asthma or significant allergic disease Use of antibiotics, antivirals, probiotics or prebiotics for more than 48h within 2 weeks of study entry History of recurrent respiratory infections (>2 otitis, >1 severe sinusitis or >1 pneumonia) within 12 months of study entry History of 2 or more invasive infections (meningitis, cellulitis, osteomyelitis, sepsis) Chronic diarrhea or short bowel syndrome Congenital heart or respiratory deficiency Known alpha1-antitrypsin deficiency Concurrent participation in other clinical trial(s) Other particular conditions which, in the judgment of the Principal Investigator, may interfere with the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedro Gutierrez-Castrellon, MD, PhD
Organizational Affiliation
Hospital General Dr. Manuel Gea Gonzalez
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital General Dr. Manuel Gea Gonzalez
City
Mexico City
State/Province
Mexico DF
ZIP/Postal Code
14080
Country
Mexico

12. IPD Sharing Statement

Citations:
PubMed Identifier
12723828
Citation
Manworren RC, Hynan LS. Clinical validation of FLACC: preverbal patient pain scale. Pediatr Nurs. 2003 Mar-Apr;29(2):140-6.
Results Reference
background
PubMed Identifier
35014600
Citation
Gutierrez-Castrellon P, Gandara-Marti T, Abreu Y Abreu AT, Nieto-Rufino CD, Lopez-Orduna E, Jimenez-Escobar I, Jimenez-Gutierrez C, Lopez-Velazquez G, Espadaler-Mazo J. Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gut Microbes. 2022 Jan-Dec;14(1):2018899. doi: 10.1080/19490976.2021.2018899.
Results Reference
background
PubMed Identifier
33789556
Citation
Maya-Barrios A, Lira-Hernandez K, Jimenez-Escobar I, Hernandez L, Ortiz-Hernandez A, Jimenez-Gutierrez C, Lopez-Velazquez G, Gutierrez-Castrellon P. Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 as adjuvants to improve evolution of pharyngitis/tonsillitis in children: randomised controlled trial. Benef Microbes. 2021 Apr 12;12(2):137-145. doi: 10.3920/BM2020.0171. Epub 2021 Apr 1.
Results Reference
background
PubMed Identifier
9220806
Citation
Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.
Results Reference
background

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Efficacy and Safety of L. Plantarum and P. Acidilactici in Children With Upper Respiratory Tract Infections

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