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

Pharyngitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05279534
• Other study ID #: PROPED-URTI
• Status: Terminated
• Phase: N/A
• Start date: March 8, 2022
• Est. completion date: June 2, 2023

Study information

• Verified date: October 2023
• Source: AB Biotics, SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: June 2, 2023
• Est. primary completion date: June 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 5 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Pharyngitis
• Respiratory Tract Infections
• Tonsillitis
• Upper Respiratory Tract Infections

Intervention

Dietary Supplement:
• Probiotic
Combination of strains Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, twice daily for 15 days

Other:
• Placebo
Combination of maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0, twice daily for 15 days

Locations

Country	Name	City	State
Mexico	Hospital General Dr. Manuel Gea Gonzalez	Mexico City	Mexico DF

Sponsors (3)

Lead Sponsor	Collaborator
AB Biotics, SA	Hospital General Dr. Manuel Gea González, Innovacion y Desarrollo de Estrategias en Salud

Country where clinical trial is conducted

Mexico, 

References & Publications (4)

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. — View Citation

Manworren RC, Hynan LS. Clinical validation of FLACC: preverbal patient pain scale. Pediatr Nurs. 2003 Mar-Apr;29(2):140-6. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Etiology of the upper respiratory tract infection at baseline	Identification of the viral or bacterial pathogen responsible for the baseline episode of upper respiratory tract infection by molecular methods	Day 1
Other	Salivary vitamin D at baseline	Concentration of vitamin D at baseline as measured in saliva sample	Day 1
Primary	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	Day 1 to 15
Primary	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	Day 1 to 15
Secondary	Fever Area Under the Curve	Area Under the Curve (AUC) of daily fever (body temperature, Celsius degrees)	Day 1 to 60
Secondary	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])	Day 1 to 60
Secondary	Days with fever	Days with body temperature > 37.5 Celsius, as noted in patient diary	Day 1 to 60
Secondary	Days with pain	Days with pain as per FLACC scale (Face, Legs, Activity, Cry and Consolability), as noted in patient diary	Day 1 to 60
Secondary	Days with rhinorrhea	Days with runny nose, as noted in patient diary	Day 1 to 60
Secondary	Days with cough	Days of cough, as noted in patient diary	Day 1 to 60
Secondary	Days with nasal congestion	Days of nasal congestion, as noted in patient diary	Day 1 to 60
Secondary	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)	Day 1 to 60
Secondary	Days with concomitant medication	Days of intake of NSAIDS (non-steroidal anti-inflammatory drugs) and/or antihistamines, as noted in patient diary	Day 1 to 60
Secondary	Number of children receiving antibiotics	Number of children receiving antibiotics	Day 1 to 60
Secondary	Number of hospitalizations	Number of children being hospitalized related to respiratory tract infection	Day 1 to 60
Secondary	Number of medical or emergency visits	Number of medical or emergency visits related to respiratory tract infection	Day 1 to 60
Secondary	Days of schooling absence	Days of daycare or kindergarten absence, as noted in patient diary	Day 1 to 60
Secondary	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	Day 1 to 15
Secondary	Total treatment costs	Cost of medical and emergency visits, drug treatments (anti-inflammatory drugs, anti-histamines and antibiotics) and schooling absence	Day 1 to 60
Secondary	Time to fever resolution	Time to body temperature at or below 37.5 Celsius, as noted in patient diary	Day 1 to 15
Secondary	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	Day 1 to 15
Secondary	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	Day 1 to 15
Secondary	Time to fever recurrence	Time to body temperature >37.5 Celsius after initial resolution (see outcome #19), as noted in patient diary	Day 15 to 60
Secondary	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	Day 15 to 60
Secondary	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	Day 15 to 60
Secondary	Change in microbiota	Change in microbiota composition, as determined by 16S gene sequencing	Day 1 to 15