Evaluation of Safety and Human Tolerance of Oral Probiotic Streptococcus Salivarius eK12

NCT06380270 | Completed DMC

• 1 other identifier: MMC/ERC/03.03.2025
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The human oral cavity contains a diverse community of microorganisms essential for oral and overall health. Streptococcus salivarius K12 (eK12) has emerged as a promising oral probiotic due to its natural colonization of the throat and its ability to inhibit pathogens such as Streptococcus pyogenes, a major cause of streptococcal pharyngitis. It supports oral hygiene by producing antimicrobial substances like salivaricins and inhibiting odor-causing bacteria. The engineered eK12 variant (Bactoblis® Evol) has been developed to overcome inactivation by GAS-secreted protease SpeB, thereby enhancing its prophylactic potential against Group A Streptococcus (GAS) colonization. This clinical study includes a randomized, double-blind, placebo-controlled trial in Pakistan to evaluate the safety and human tolerance of eK12 in healthy adults. To enhance generalizability, an additional open-label cohort of healthy adults in Italy will receive eK12 without a control group.

Conditions

Safety; Tolerability

Outcome Measures

Primary Outcomes (15)

• Effect on oral health physical condition

  Incidence of physical abnormality in pharynx, tongue, teeth, gums and oral mucosa

  3-months

• Effect on other physical features

  Incidence of any physical abnormality in the skin, eyes, ears, nose, throat, and mental health

  3-months

• Effect on vital signs

  Any changes in the heart rate (heart beats per minute (bpm))

  3-months

• Effect on vital signs

  Any changes in the respiratory rate (number of breaths per minute)

  3-months

• Effect on vital signs

  Any changes in the blood pressure (both systolic pressure and diastolic pressure)

  3-months

• Effect on vital signs

  Any changes in the body temperature

  3-months

• Effect on blood biochemistry

  Any changes in the liver function tests (Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase)

  3-months

• Effect on blood biochemistry

  Any changes in the renal function tests (serum creatinine, serum urea, blood urea nitrogen)

  3-months

• Effect on blood biochemistry

  Any changes in the lipid profile tests (serum total cholesterol, serum triglycerides, serum high density lipoprotein-cholesterol, serum low density lipoprotein-cholesterol)

  3-months

• Effect on blood biochemistry

  Any changes in the blood glucose levels

  3-months

• Effect on blood electrolytes balance

  Electrolyte tests (e.g., sodium, potassium, chloride, bicarbonate)

  3-months

• Effect on hematology

  Full blood count

  3-months

• Incidence of inflammation

  C-recative protein (CRP) blood test

  3-months

• Incidence of gastrointestinal side effects

  Abdominal pain, bloating, gastric reflux, nausea, vomiting, diarrhea, and gas or flatulence

  3-months

• Incidence of Adverse events (AEs)

  Any adverse events that may occur during the study period

  3-months

Study Arms (2)

Probiotic supplement group

EXPERIMENTAL

Participants in this arm will daily receive 2 orally dissolving tablets (single administration) of probiotic Streptococcus salivarius eK12 (Bactoblis® EVOL: containing ca. 10 billion CFU of S. salivarius eK12) for 28-days.

Dietary Supplement: Oral probiotic Streptococcus salivarius eK12

Control group

PLACEBO COMPARATOR

Participants in this arm will daily receive 2 orally dissolving placebo tablets (single administration) for 28-days.

Other: Placebo

Interventions

Oral probiotic Streptococcus salivarius eK12 DIETARY_SUPPLEMENT

Bactoblis® EVOL (containing 10 billion CFU of S. salivarius eK12)

Probiotic supplement group

Placebo OTHER

Orally dissolving placebo tablets

Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults, both male and female, aged 18 to 60 years.
• Stable health condition with no acute illness at the time of enrollment.
• BMI 18.5-35 kg/m2
• No known food allergies or intolerances to probiotics
• All clinical chemistry, hematology and urinalysis parameters and vital signs (blood pressure, respiratory rate, temperature, heart rate) within clinically acceptable ranges.
• Ability and willingness to provide informed consent.
• Must be willing to comply with study procedures and attend scheduled visits.

You may not qualify if:

• Individuals with a history of severe allergies or adverse reactions to probiotics or any of the components of the study product.
• Participants with a recent history of oral surgery or dental procedures within the past 4 weeks.
• Individuals with severe dental problems or undergoing active dental treatment.
• Individuals with a known diagnosis of systemic diseases affecting the oral cavity (e.g., oral cancer, Sjögren's syndrome).
• Individuals with compromised immune systems, or a history of immunodeficiency disorders or undergoing immunosuppressive therapy.
• Pregnant or breastfeeding females.
• Current smokers or individuals who have quit smoking within the past 6 months.
• Individuals currently using antibiotics or have used them within the past 4 weeks.
• Individuals with a history of gastrointestinal disorders (e.g., inflammatory bowel disease, irritable bowel syndrome).
• Individuals with unstable metabolic diseases/disorders, heart failure or a history of endocarditis.
• Frequent user of alcohol or over the counter laxatives, or herbal-based supplements (but not vitamin supplements), or prescription drugs that may potentially influence the biomarkers to be measured in the study.
• Those with any chronic systemic illness that might affect participation in the trial or interpretation of results.
• Participants currently enrolled in another clinical trial involving probiotics or oral health interventions.
• Those unable to adhere to the study protocol or unlikely to complete the study period due to anticipated relocation or other personal reasons.
• Any other condition or circumstances that, in the opinion of the investigator, might compromise the safety of the participant or the validity of the study results.

Sponsors & Collaborators

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

Study Sites (1)

Jam Ghulam Qadir Civil Hospital

Hub, 90250, Pakistan

Location

Related Publications (1)

• 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 DERIVED

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 14, 2024
• First Posted: April 23, 2024
• Study Start: November 1, 2024
• Primary Completion: August 25, 2025
• Study Completion: August 25, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)