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

Not Applicable

Active, not recruiting

• Conditions: Safety; Tolerability

• Registration Number: NCT06380270
• Lead Sponsor: Liaquat University of Medical & Health Sciences

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.

Detailed Description

The aim of the present clinical study is to evaluate the safety and tolerability of Streptococcus salivarius eK12 in healthy adults. The study consists of a randomized, double-blind, placebo-controlled arm in Pakistan involving 29 participants (allocated 1:1 to eK12 or placebo).

In addition, an open-label cohort of 20 healthy adults will be enrolled in Italy, all of whom will receive eK12, to assess tolerability in a separate population without a control group. This complementary cohort is included to enhance the generalizability of the findings across different populations and to obtain supportive safety data in a real-world setting where the product (commercially available in the EU as Bactoblis® Evol) is already in use.

Through comprehensive assessments and close monitoring of participants, this study will provide critical insights into the safety profile and human tolerance of the probiotic-modified strain. The findings will contribute to the growing body of knowledge needed to support its use in oral health management.

Study Timeline

• Study First Submitted: 2024-04-14
• Study First Submitted QC: 2024-04-18
• Study First Posted: 2024-04-23
• Study Start: 2024-11-01
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-19
• Last Update Posted: 2025-06-25
• Primary Completion: 2025-08-31
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Effect on other physical features	3-months	Incidence of any physical abnormality in the skin, eyes, ears, nose, throat, and mental health
Effect on blood electrolytes balance	3-months	Electrolyte tests (e.g., sodium, potassium, chloride, bicarbonate)
Incidence of inflammation	3-months	C-recative protein (CRP) blood test
Effect on oral health physical condition	3-months	Incidence of physical abnormality in pharynx, tongue, teeth, gums and oral mucosa
Effect on hematology	3-months	Full blood count
Effect on vital signs	3-months	Any changes in the body temperature
Effect on blood biochemistry	3-months	Any changes in the blood glucose levels
Incidence of gastrointestinal side effects	3-months	Abdominal pain, bloating, gastric reflux, nausea, vomiting, diarrhea, and gas or flatulence
Incidence of Adverse events (AEs)	3-months	Any adverse events that may occur during the study period

Trial Locations

Locations (1)

Liaquat University of Medical & Health Sciences (LUMHS); 🇵🇰 Jāmshoro, Pakistan