Safety, Tolerability
Conditions
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.
Interventions
DIETARY_SUPPLEMENTOral probiotic Streptococcus salivarius eK12
Bactoblis® EVOL (containing 10 billion CFU of S. salivarius eK12)
OTHERPlacebo
Orally dissolving placebo tablets
Sponsors
Università degli Studi dell'Insubria
Liaquat University of Medical & Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect on oral health physical condition | 3-months | Incidence of physical abnormality in pharynx, tongue, teeth, gums and oral mucosa |
| Effect on other physical features | 3-months | Incidence of any physical abnormality in the skin, eyes, ears, nose, throat, and mental health |
| Effect on vital signs | 3-months | Any changes in the heart rate (heart beats per minute (bpm)) |
| Effect on blood biochemistry | 3-months | Any changes in the liver function tests (Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) |
| Effect on blood electrolytes balance | 3-months | Electrolyte tests (e.g., sodium, potassium, chloride, bicarbonate) |
| Effect on hematology | 3-months | Full blood count |
| Incidence of inflammation | 3-months | C-recative protein (CRP) blood test |
| 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 |
Countries
Pakistan
Outcome results
None listed