Prophylactic Effect of Probiotic Streptococcus Salivarius eK12 Against Recurrent Streptococcus Pyogenes Pharyngotonsillitis Infection in Pediatrics

NCT06370208 | Recruiting DMC

• 1 other identifier: LUMHS/REC/-496/11.11.2024
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent Group A Streptococcus (GAS) infections, primarily presenting as strep throat, are a significant health concern in pediatric populations, leading to symptoms like sore throat, fever, and swollen lymph nodes. GAS is highly contagious and can spread easily among children in close-contact environments like schools and daycare centers, often resulting in frequent re-infections. Managing these recurrent infections typically requires antibiotics, but reliance on antibiotics carries risks, including resistance development, gut microbiota disruption, and various side effects. Probiotic therapy, particularly with Streptococcus salivarius K12, has shown promise as a preventive approach, utilizing competitive exclusion and antimicrobial production to inhibit GAS growth in the oral cavity. Recent studies have advanced this with the development of S. salivarius eK12, a re-engineered strain that enhances efficacy against GAS by preventing the survival-promoting interactions between the probiotic and pathogenic bacteria. This modified strain, now registered as Bactoblis® EVOL in Italy (EU), holds potential as an effective version to reduce the incidence and severity of GAS infections without the drawbacks of antibiotic therapy.

Conditions

Streptococcus Pyogenes Pharyngotonsillitis

Outcome Measures

Primary Outcomes (2)

• Recurrence of Streptococcus pyogenes pharyngotonsillitis infection

  Number of episodes of Streptococcus pyogenes pharyngotonsillitis infection

  6-months

• Probiotic safety and tolerability

  Incidences of any side effects

  6-months

Secondary Outcomes (7)

• Protection against viral infection

  6-months

• Protection against Acute Otitis Media infection

  6-months

• Protection against respiratory infection

  6-months

• Protection against Rhinitis

  6-months

• Protection against flu

  6-months

Study Arms (2)

Probiotic supplement group

EXPERIMENTAL

Participants in this group will receive probiotic Streptococcus salivarius eK12 (Bactoblis® EVOLcontaining ca. 1 billion CFU of Streptococcus salivarius eK12/capsule) as daily one capsule (to be slowly dissolved in the mouth before sleeping at night time) for 3-months. There will be a further 3-months follow-up period.

Dietary Supplement: Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12)

Control group

NO INTERVENTION

Participants in this group will not receive probiotic Streptococcus salivarius eK12 (Bactoblis® EVOL).

Interventions

Probiotic Bactoblis® EVOL (Streptococcus salivarius eK12) DIETARY_SUPPLEMENT

Bactoblis® EVOL: containing one billion CFU of probiotic Streptococcus salivarius eK12

Probiotic supplement group

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 3-10 years.
• Recent history of documented recurrent episodes of Streptococcus pyogenes pharyngo- tonsillitis infection in the last 6 months, or 4 or more episodes in the last 12 months (S.
• pyogenes infection being defined as: McIsaac score with clinical score ≥ 2 plus confirmation of S. pyogenes presence with rapid throat swab (RAD) method or McIsaac score =5.
• Willingness to comply with the study protocol and attend scheduled follow-up visits.
• Written informed consent obtained from the parent or legal guardian.

You may not qualify if:

• Children with known allergies or hypersensitivity to probiotics or any components of the study product.
• Current use of antibiotics or within the past 30 days.
• Used oral colonizing probiotics in the last 6 months.
• Presence of severe underlying medical conditions affecting the immune system or gastrointestinal tract.
• Participation in other clinical trials involving investigational drugs or interventions.
• Inability to adhere to the study requirements due to logistical or social reasons.
• History of rheumatic disorders, bronchospasm, severe asthma, or allergy requiring corticosteroids.
• Past tonsillectomy or an indication for adeno-tonsillectomy; or severe respiratory or systemic disorders
• Individuals immunocompromised or had a condition favouring recurrent Acute Otitis Media (AOM), including severe atopy, acquired or congenital immunodeficiency, cleft palate, craniofacial abnormalities, obstructive adenoids, a chronically ruptured eardrum, sleep apnoea, or tympanostomy tubes
• Children undergoing current pharmacological therapies to prevent recurrent respiratory infections.
• Any other medical condition or circumstance that, in the investigator's judgment, would compromise the safety of the participant or the integrity of the study.

Sponsors & Collaborators

• Liaquat University of Medical & Health Sciences: lead
• Università degli Studi dell'Insubria: collaborator

Study Sites (1)

Liaquat University of Medical and Health Sciences

Jamshoro, 76090, Pakistan

RECRUITING

Related Publications (6)

• Di Pierro F, Veeraraghavan G, Kalaiselvan K, Ashif B, Jeyakumar L, Gopalakrishnan G, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Ujjan I, Bugti AA, Bano A, Gull Y, Mumtaz N, Khan A. In Vitro and In Vivo Safety Evaluation of Streptococcus salivarius eK12, a Genetically Modified Dietary Probiotic Derived from the Oral Probiotic S. salivarius K12. J Microbiol Biotechnol. 2025 Dec 9;35:e2509016. doi: 10.4014/jmb.2509.09016.

  PMID: 41391486 BACKGROUND

• Di Pierro F, Bugti AA, Bano A, Kara M, Ujjan I, Mumtaz N, Gull Y, Cazzaniga M, Bertuccioli A, Tanda ML, Zerbinati N, Hameed S, Khan A. Study to evaluate the safety and tolerability of Streptococcus salivarius eK12, a genetically modified strain derived from the oral probiotic S. salivarius K12: Results from a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Front Nutr. 2025 Dec 8;12:1701611. doi: 10.3389/fnut.2025.1701611. eCollection 2025.

  PMID: 41438195 BACKGROUND

• Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016 Nov;20(21):4601-4606.

  PMID: 27874935 RESULT

• Di Pierro F, Colombo M, Zanvit A, Rottoli AS. Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: a pilot investigation. Drug Healthc Patient Saf. 2016 Nov 21;8:77-81. doi: 10.2147/DHPS.S117214. eCollection 2016.

  PMID: 27920580 RESULT

• Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014 Feb 13;6:15-20. doi: 10.2147/DHPS.S59665. eCollection 2014.

  PMID: 24600248 RESULT

• Di Pierro F, Donato G, Fomia F, Adami T, Careddu D, Cassandro C, Albera R. Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media. Int J Gen Med. 2012;5:991-7. doi: 10.2147/IJGM.S38859. Epub 2012 Nov 30.

  PMID: 23233809 RESULT

Related Links

• Related Info

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Biochemistry and Experimental Medicine

Study Record Dates

• First Submitted: April 13, 2024
• First Posted: April 17, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)