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Completed

NCT Number: NCT06380270

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

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.

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Key information

Conditions

Safety Tolerability

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Jam Ghulam Qadir Civil Hospital

Hub, 90250, Pakistan

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oral probiotic Streptococcus salivarius eK12

Dietary Supplement

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

Placebo

Other

Orally dissolving placebo tablets

Primary outcomes

  1. Effect on oral health physical condition

    Time frame: 3-months

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

  2. Effect on other physical features

    Time frame: 3-months

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

  3. Effect on vital signs

    Time frame: 3-months

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

  4. Effect on vital signs

    Time frame: 3-months

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

  5. Effect on vital signs

    Time frame: 3-months

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

  6. Effect on vital signs

    Time frame: 3-months

    Any changes in the body temperature

  7. Effect on blood biochemistry

    Time frame: 3-months

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

  8. Effect on blood biochemistry

    Time frame: 3-months

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

  9. Effect on blood biochemistry

    Time frame: 3-months

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

  10. Effect on blood biochemistry

    Time frame: 3-months

    Any changes in the blood glucose levels

  11. Effect on blood electrolytes balance

    Time frame: 3-months

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

  12. Effect on hematology

    Time frame: 3-months

    Full blood count

  13. Incidence of inflammation

    Time frame: 3-months

    C-recative protein (CRP) blood test

  14. Incidence of gastrointestinal side effects

    Time frame: 3-months

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

  15. Incidence of Adverse events (AEs)

    Time frame: 3-months

    Any adverse events that may occur during the study period

Sponsors and collaborators

Lead sponsor

Liaquat University of Medical & Health Sciences

Other

Collaborators

  • Università degli Studi dell'Insubria

Registry information

Official study title

Study to Evaluate the Safety and Human Tolerance of the Oral Probiotic Streptococcus Salivarius eK12: A Randomized, Double-blind Clinical Trial

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Apr 23, 2024
Registry last updated
Sep 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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