SafetyNCT06380270
Evaluation of Safety and Human Tolerance of Oral Probiotic Streptococcus Salivarius eK12
A study testing Oral probiotic Streptococcus salivarius eK12 in people with Safety and Tolerability, run by Liaquat University of Medical & Health Sciences at 1 site in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety, Tolerability
- What is being tested?
- Oral probiotic Streptococcus salivarius eK12
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Nov 2024to 25 Aug 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study to Evaluate the Safety and Human Tolerance of the Oral Probiotic Streptococcus Salivarius eK12: A Randomized, Double-blind Clinical Trial
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.
Read the 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
- Being tested
- Oral probiotic Streptococcus salivarius eK12, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral probiotic Streptococcus salivarius eK12Dietary supplement
Bactoblis® EVOL (containing 10 billion CFU of S. salivarius eK12)
PlaceboOther
Orally dissolving placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect on oral health physical condition
Incidence of physical abnormality in pharynx, tongue, teeth, gums and oral mucosa
Measured: 3-months
Effect on other physical features
Incidence of any physical abnormality in the skin, eyes, ears, nose, throat, and mental health
Measured: 3-months
Effect on vital signs
Any changes in the heart rate (heart beats per minute (bpm))
Measured: 3-months
Effect on vital signs
Any changes in the respiratory rate (number of breaths per minute)
Measured: 3-months
Effect on vital signs
Any changes in the blood pressure (both systolic pressure and diastolic pressure)
Measured: 3-months
Effect on vital signs
Any changes in the body temperature
Measured: 3-months
Effect on blood biochemistry
Any changes in the liver function tests (Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase)
Measured: 3-months
Effect on blood biochemistry
Any changes in the renal function tests (serum creatinine, serum urea, blood urea nitrogen)
Measured: 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)
Measured: 3-months
Effect on blood biochemistry
Any changes in the blood glucose levels
Measured: 3-months
Effect on blood electrolytes balance
Electrolyte tests (e.g., sodium, potassium, chloride, bicarbonate)
Measured: 3-months
Effect on hematology
Full blood count
Measured: 3-months
Incidence of inflammation
C-recative protein (CRP) blood test
Measured: 3-months
Incidence of gastrointestinal side effects
Abdominal pain, bloating, gastric reflux, nausea, vomiting, diarrhea, and gas or flatulence
Measured: 3-months
Incidence of Adverse events (AEs)
Any adverse events that may occur during the study period
Measured: 3-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start1 Nov 2024
- Primary completion25 Aug 2025
- Study completion25 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SafetyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liaquat University of Medical & Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli Studi dell'Insubria
- Responsible party
- Principal investigator, Dr. Amjad Khan, Liaquat University of Medical & Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06380270
- Sponsor's protocol ID
- MMC/ERC/03.03.2025
- Status last verified
- Sep 2025
- First submitted
- 14 Apr 2024
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41438195
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Safety and Human Tolerance of the Oral Probiotic Streptococcus Salivarius eK12: A Randomized, Double-blind Clinical Trial
- ClinicalTrials.gov ID
- NCT06380270
- Acronym / sponsor ID
- MMC/ERC/03.03.2025
- Conditions
- Safety, Tolerability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Liaquat University of Medical & Health SciencesUniversity, hospital or other
- Collaborators
- Università degli Studi dell'Insubria
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 25 Aug 2025 (actual)
- Study completion
- 25 Aug 2025 (actual)
- First posted
- 23 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic supplement group | Experimental | Dietary Supplement: Oral probiotic Streptococcus salivarius eK12Participants 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. |
| Control group | Placebo comparator | Other: PlaceboParticipants in this arm will daily receive 2 orally dissolving placebo tablets (single administration) for 28-days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral probiotic Streptococcus salivarius eK12Bactoblis® EVOL (containing 10 billion CFU of S. salivarius eK12) | Dietary supplement | Probiotic supplement group |
| PlaceboOrally dissolving placebo tablets | Other | Control group |
Primary outcome
Effect on oral health physical condition
Time frame: 3-months
Incidence of physical abnormality in pharynx, tongue, teeth, gums and oral mucosa
Effect on other physical features
Time frame: 3-months
Incidence of any physical abnormality in the skin, eyes, ears, nose, throat, and mental health
Effect on vital signs
Time frame: 3-months
Any changes in the heart rate (heart beats per minute (bpm))
Effect on vital signs
Time frame: 3-months
Any changes in the respiratory rate (number of breaths per minute)
Effect on vital signs
Time frame: 3-months
Any changes in the blood pressure (both systolic pressure and diastolic pressure)
Effect on vital signs
Time frame: 3-months
Any changes in the body temperature
Effect on blood biochemistry
Time frame: 3-months
Any changes in the liver function tests (Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase)
Effect on blood biochemistry
Time frame: 3-months
Any changes in the renal function tests (serum creatinine, serum urea, blood urea nitrogen)
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)
Effect on blood biochemistry
Time frame: 3-months
Any changes in the blood glucose levels
Effect on blood electrolytes balance
Time frame: 3-months
Electrolyte tests (e.g., sodium, potassium, chloride, bicarbonate)
Effect on hematology
Time frame: 3-months
Full blood count
Incidence of inflammation
Time frame: 3-months
C-recative protein (CRP) blood test
Incidence of gastrointestinal side effects
Time frame: 3-months
Abdominal pain, bloating, gastric reflux, nausea, vomiting, diarrhea, and gas or flatulence
Incidence of Adverse events (AEs)
Time frame: 3-months
Any adverse events that may occur during the study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Derived from this study: PubMed 41438195Di 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral probiotic Streptococcus salivarius eK12 in people with Safety and Tolerability, run by Liaquat University of Medical & Health Sciences at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect on oral health physical condition (time frame: 3-months). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06380270, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2025.