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

NCT ID: NCT06380270

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2025-08-25

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.

Conditions

Safety; Tolerability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Probiotic supplement group

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.

Group Type: EXPERIMENTAL

Oral probiotic Streptococcus salivarius eK12

Intervention Type: DIETARY_SUPPLEMENT

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

Control group

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Orally dissolving placebo tablets

Interventions

Oral probiotic Streptococcus salivarius eK12

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Orally dissolving placebo tablets

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Università degli Studi dell'Insubria

OTHER

Sponsor Role: collaborator

Liaquat University of Medical & Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Dr. Amjad Khan

Professor of Clinical Biochemistry and Experimental Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Jam Ghulam Qadir Civil Hospital

Hub, , Pakistan

Countries

Pakistan

Other Identifiers

MMC/ERC/03.03.2025

Identifier Type: -

Identifier Source: org_study_id