Oral DysbiosisPhase 2/3NCT05463484
Effects of a Composition on the Oral Microbiome, pH, Nitrite/Nitrate Ratio, Elastases and Inflammation in Oral Dysbiosis
A Phase 2/3 study testing Test composition Saliactive® (olive product, betaine and xylitol) in people with Oral Dysbiosis, run by Mucosa Innovations, S.L. at 1 site in Spain.
Trial summary
Dysbiosis is a condition in which the normal function of an ecological net is altered. In dysbiosis a state of inflammation, a loss of hydration, a change in pH, a loss of the barrier function are all allies of key pathogens that initiate invasion and cytokine and pro-inflammatory mediators release that target other… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Oral Dysbiosis
- What is being tested?
- Test composition Saliactive® (olive product, betaine and xylitol)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSpain
- Study dates
- 13 Jul 2021to 15 Jul 2023
- Phase
- Phase 2/3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnose of gingivitis.
- At least 20 teeth (3rd molars excluded).
- Must Accept informed consent.
Who cannot join
- Clinical diagnose of periodontitis.
- With orthodontics.
- With removable dentures.
- With upper incisors restorated.
- Tumours in soft or hard tissues of the mouth.
- More than 5 caries lesions with immediate restorative need
Show all 10Show fewer
- Antibiotics intake less than one month ago.
- Pregnant women.
- Other clinic assay at the moment.
- Dental prophylaxis less than 2 weeks before starting the study.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Departamento de Estomatología, Facultad de Odontología
Granada, 18071
About this study
Official title: Effects of a Composition Delivered Via Toothpaste on the Oral Microbiome, pH, Nitrite/Nitrate Ratio, Elastases, and Inflammation in Patients With Oral Dysbiosis: A Controlled, Randomized, Double-blind Study. Part of Stop Dysbiosis Project
Dysbiosis is a condition in which the normal function of an ecological net is altered. In dysbiosis a state of inflammation, a loss of hydration, a change in pH, a loss of the barrier function are all allies of key pathogens that initiate invasion and cytokine and pro-inflammatory mediators release that target other tissues and organs resulting in chronic inflammatory conditions.
In health there is a cross-talk between the host and the microbiota in order to maintain and promote a state of eubiosis with a local and general health gain. Dysbiosis reversion has not been solved with the use of antibacterials, antiseptics nor antibiotics.
Read more
Stop dysbiosis project is focussed on different aspects of human dysbiosis such as oral dysbiosis, skin dysbiosis, vaginal dysbiosis and cancer dysbiosis, between others including the current prospective interventional double-blind randomised clinical trial.
One of the most common oral dysbiosis is periodontal and mucosa dysbiosis that courses with inflammation of the gingiva (gingivitis). This inflammation induces specific enzymes that in a later stage destroy connective tissue. The current clinical trial analyzes the effect of a composition (Saliactive ®) delivered to the oral cavity via a daily use toothpaste (YOTUEL® microbiome toothpaste) in a group of patients with oral dysbiosis.
Read the detailed description
Oral microbiota is the most diverse of the human body. It consists of mainly commensal bacteria, archea, protozoos, yeast and funghi. More than 700 species of bacteria have been identified in the mouth. In conditions of health these bacteria live in equilibrium. In inflammatory conditions, balance is lost, due to changes in microbiota or in the ecosystem with lost of the mucosa barrier function. If dysbiosis appears pathogen or fragments of these or toxic agents penetrate the body orchestrating a deep alteration of vital functions such as immune defense, nitric oxide pathways, cell cycle regulation and redox balance.
Periodontal dysbiosis is the consequence of the accumulation of plaque and the increase of gram negative species capable of releasing virulence factors that maintain inflammation and bleeding that perpetuate a disease-promoting ecosystem.
Oral hygiene is a daily personal protocol for effective delivery of active substances to the tissues of the oral cavity, mainly fluoride and antiseptics. The standard of care in the oral compound is toothpaste used 2-3 times a day.
The test toothpaste including Saliactive® (an olive product, betaine and xylitol) does not contain any antimicrobial agent nor antiseptic. A randomized, double-blind controlled clinical trial in 100 patients will evaluate the efficacy to reverse oral dysbiosis. Microbiota profile through genetic sequenciation of the rDNA16s, inflammatory markers, nitrate reducing bacteria abundance, nitrite/nitrate ratio, pH, plaque and bleeding index will be evaluated at baseline, after 2 months and 4 months of exposure to the assigned composition. Two controls will be analysed, one fluoridated placebo but without the 3 active ingredients olive product, betaine and xylitol (Saliactive®), and a fluoridated commercial toothpaste for gingivitis with zinc citrate. Assignation of the 100 subjects will be randomized and the products are blind for the subjects and the researcher.
- Conditions
- Oral Dysbiosis
- Being tested
- Test composition Saliactive® (olive product, betaine and xylitol), Placebo, Control
- Keywords
- Gum inflammation, Periodontal Dysbiosis, Oral Dysbiosis
- Medical subject headings
- Gingivitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Test composition Saliactive® (olive product, betaine and xylitol)Drug
Also called Saliactive®
Fluoridated toothpaste with Saliactive®.
PlaceboDrug
Also called Placebo fluoridated toothpaste without the test composition
Fluoridated toothpaste without Saliactive®.
ControlDrug
Also called Control commercial Fluoridated toothpaste for gingivitis with zinc citrate.
Commercial Fluoridated toothpaste for gingivitis with zinc citrate.
| Study group | Role | What they receive |
|---|---|---|
| Test product | Experimental | Toothpaste including an olive product, betaine and xylitol (Saliactive®). Receives: Drug: Test composition Saliactive® (olive product, betaine and xylitol) |
| Placebo product | Placebo comparator | Toothpaste with the same composition as the test product but without olive product, betaine and xylitol. Receives: Drug: Placebo |
| Control product | Active comparator | Toothpaste marketed for gingivitis with zinc mineral with antimicrobial activity. Receives: Drug: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral microbiota profile at baseline and after 4 months
16s rDNA genetic sequencing
Measured: 4 months
Oral pH at baseline and after 4 months
pH meter
Measured: 4 months
Nitrite/Nitrate ratio at baseline and after 4 months
Ionic chromatography
Measured: 4 months
Elastase at baseline at 2 months and at 4 months
ELISA
Measured: 4 months
Bleeding index at baseline, at 2 months and at 4 months
Ainamo and Bay bleeding index indicating the percentage of bleeding from 0 (no bleeding) to 100 (maximum bleeding)
Measured: 4 months
Plaque index at baseline, at 2 months and at 4 months
Tonetti plaque index
Measured: 4 months
Secondary outcomes (1)
Salivary flow rate at baseline, 2 months and at 4 months
Unstimulated salivary flow rate recovery as per Navazesh
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study start13 Jul 2021
- Primary completion28 Feb 2023
- Study completion15 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Oral DysbiosisStudies 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 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three toothpastes will be included in the study; one with the composition including an olive product, betaine and xylitol, one with the same composition but without the olive product, betaine and xylitol, and one of a product marketed for gingivitis with and antimicrobial ingredient. Subjects are randomnly assigned and products will have a white label so that nor subject nor researcher will know the composition to be tested.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mucosa Innovations, S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Universidad de Granada
- Responsible party
- Sponsor
- Investigators
- Francisco Luis Mesa Aguado, Principal investigator, Departamento de Estomatología, Facultad de Odontología
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05463484
- Sponsor's protocol ID
- 02-2021
- Status last verified
- Jul 2024
- First submitted
- 7 Jul 2022
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tonetti MS. The future of periodontology: new treatments for a new era. J Int Acad Periodontol. 2002 Jul;4(3):110-4.
PubMed 12670090Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975 Dec;25(4):229-35.
PubMed 1058834Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993 Sep 20;694:72-7. doi: 10.1111/j.1749-6632.1993.tb18343.x. No abstract available.
PubMed 8215087Barbadoro P, Ponzio E, Coccia E, Prospero E, Santarelli A, Rappelli GGL, D'Errico MM. Association between hypertension, oral microbiome and salivary nitric oxide: A case-control study. Nitric Oxide. 2021 Jan 1;106:66-71. doi: 10.1016/j.niox.2020.11.002. Epub 2020 Nov 10.
PubMed 33186726Bescos R, Ashworth A, Clarke C, Brookes ZL, Belfield L, Rodiles A, Casas-Agustench P, Farnham G, Liddle L, Burleigh M, White D, Easton C, Hickson M. Effects of Chlorhexidine mouthwash on the oral microbiome. Sci Rep. 2020 Mar 24;10(1):5254. doi: 10.1038/s41598-020-61912-4.
PubMed 32210245Mesa F, Rodriguez-Agurto A, Bonilla M, Rodriguez-Vilaboa D, Rodriguez-Vilaboa B, Bravo M. Betaine-, xylitol-, and extra virgin olive oil-based toothpaste modulates inflammation and oral nitric oxide pathway: Clinical trial in gingivitis. J Periodontol. 2026 Apr 14. doi: 10.1002/jper.70135. Online ahead of print.
PubMed 41981946
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a Composition Delivered Via Toothpaste on the Oral Microbiome, pH, Nitrite/Nitrate Ratio, Elastases, and Inflammation in Patients With Oral Dysbiosis: A Controlled, Randomized, Double-blind Study. Part of Stop Dysbiosis Project
- ClinicalTrials.gov ID
- NCT05463484
- Acronym / sponsor ID
- 02-2021
- Conditions
- Oral Dysbiosis
- Keywords
- Gum inflammation, Periodontal Dysbiosis, Oral Dysbiosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Mucosa Innovations, S.L.Industry (pharma, biotech, devices)
- Collaborators
- Universidad de Granada
- Study start
- 13 Jul 2021 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 15 Jul 2023 (actual)
- First posted
- 19 Jul 2022 (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.
Dysbiosis is a condition in which the normal function of an ecological net is altered. In dysbiosis a state of inflammation, a loss of hydration, a change in pH, a loss of the barrier function are all allies of key pathogens that initiate invasion and cytokine and pro-inflammatory mediators release that target other tissues and organs resulting in chronic inflammatory conditions.
In health there is a cross-talk between the host and the microbiota in order to maintain and promote a state of eubiosis with a local and general health gain. Dysbiosis reversion has not been solved with the use of antibacterials, antiseptics nor antibiotics.
Stop dysbiosis project is focussed on different aspects of human dysbiosis such as oral dysbiosis, skin dysbiosis, vaginal dysbiosis and cancer dysbiosis, between others including the current prospective interventional double-blind randomised clinical trial.
One of the most common oral dysbiosis is periodontal and mucosa dysbiosis that courses with inflammation of the gingiva (gingivitis). This inflammation induces specific enzymes that in a later stage destroy connective tissue. The current clinical trial analyzes the effect of a composition (Saliactive ®) delivered to the oral cavity via a daily use toothpaste (YOTUEL® microbiome toothpaste) in a group of patients with oral dysbiosis.
Detailed description
Oral microbiota is the most diverse of the human body. It consists of mainly commensal bacteria, archea, protozoos, yeast and funghi. More than 700 species of bacteria have been identified in the mouth. In conditions of health these bacteria live in equilibrium. In inflammatory conditions, balance is lost, due to changes in microbiota or in the ecosystem with lost of the mucosa barrier function. If dysbiosis appears pathogen or fragments of these or toxic agents penetrate the body orchestrating a deep alteration of vital functions such as immune defense, nitric oxide pathways, cell cycle regulation and redox balance.
Periodontal dysbiosis is the consequence of the accumulation of plaque and the increase of gram negative species capable of releasing virulence factors that maintain inflammation and bleeding that perpetuate a disease-promoting ecosystem.
Oral hygiene is a daily personal protocol for effective delivery of active substances to the tissues of the oral cavity, mainly fluoride and antiseptics. The standard of care in the oral compound is toothpaste used 2-3 times a day.
The test toothpaste including Saliactive® (an olive product, betaine and xylitol) does not contain any antimicrobial agent nor antiseptic. A randomized, double-blind controlled clinical trial in 100 patients will evaluate the efficacy to reverse oral dysbiosis. Microbiota profile through genetic sequenciation of the rDNA16s, inflammatory markers, nitrate reducing bacteria abundance, nitrite/nitrate ratio, pH, plaque and bleeding index will be evaluated at baseline, after 2 months and 4 months of exposure to the assigned composition. Two controls will be analysed, one fluoridated placebo but without the 3 active ingredients olive product, betaine and xylitol (Saliactive®), and a fluoridated commercial toothpaste for gingivitis with zinc citrate. Assignation of the 100 subjects will be randomized and the products are blind for the subjects and the researcher.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Three toothpastes will be included in the study; one with the composition including an olive product, betaine and xylitol, one with the same composition but without the olive product, betaine and xylitol, and one of a product marketed for gingivitis with and antimicrobial ingredient. Subjects are randomnly assigned and products will have a white label so that nor subject nor researcher will know the composition to be tested.
| Arm | Type | Receives |
|---|---|---|
| Test product | Experimental | Drug: Test composition Saliactive® (olive product, betaine and xylitol)Toothpaste including an olive product, betaine and xylitol (Saliactive®). |
| Placebo product | Placebo comparator | Drug: PlaceboToothpaste with the same composition as the test product but without olive product, betaine and xylitol. |
| Control product | Active comparator | Drug: ControlToothpaste marketed for gingivitis with zinc mineral with antimicrobial activity. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical diagnose of gingivitis.
- At least 20 teeth (3rd molars excluded).
- Must Accept informed consent.
Key exclusion criteria (10 listed)
- Clinical diagnose of periodontitis.
- With orthodontics.
- With removable dentures.
- With upper incisors restorated.
- Tumours in soft or hard tissues of the mouth.
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 |
|---|---|---|
| Test composition Saliactive® (olive product, betaine and xylitol)Also: Saliactive®Fluoridated toothpaste with Saliactive®. | Drug | Test product |
| PlaceboAlso: Placebo fluoridated toothpaste without the test compositionFluoridated toothpaste without Saliactive®. | Drug | Placebo product |
| ControlAlso: Control commercial Fluoridated toothpaste for gingivitis with zinc citrate.Commercial Fluoridated toothpaste for gingivitis with zinc citrate. | Drug | Control product |
Primary outcome
Oral microbiota profile at baseline and after 4 months
Time frame: 4 months
16s rDNA genetic sequencing
Oral pH at baseline and after 4 months
Time frame: 4 months
pH meter
Nitrite/Nitrate ratio at baseline and after 4 months
Time frame: 4 months
Ionic chromatography
Elastase at baseline at 2 months and at 4 months
Time frame: 4 months
ELISA
Bleeding index at baseline, at 2 months and at 4 months
Time frame: 4 months
Ainamo and Bay bleeding index indicating the percentage of bleeding from 0 (no bleeding) to 100 (maximum bleeding)
Plaque index at baseline, at 2 months and at 4 months
Time frame: 4 months
Tonetti plaque index
1 secondary outcome
Salivary flow rate at baseline, 2 months and at 4 months
Time frame: 4 months
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 8 Jul 2024.
- Background: PubMed 12670090Tonetti MS. The future of periodontology: new treatments for a new era. J Int Acad Periodontol. 2002 Jul;4(3):110-4.
- Background: PubMed 1058834Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975 Dec;25(4):229-35.
- Background: PubMed 8215087Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci. 1993 Sep 20;694:72-7. doi: 10.1111/j.1749-6632.1993.tb18343.x. No abstract available.
- Background: PubMed 33186726Barbadoro P, Ponzio E, Coccia E, Prospero E, Santarelli A, Rappelli GGL, D'Errico MM. Association between hypertension, oral microbiome and salivary nitric oxide: A case-control study. Nitric Oxide. 2021 Jan 1;106:66-71. doi: 10.1016/j.niox.2020.11.002. Epub 2020 Nov 10.
- Background: PubMed 32210245Bescos R, Ashworth A, Clarke C, Brookes ZL, Belfield L, Rodiles A, Casas-Agustench P, Farnham G, Liddle L, Burleigh M, White D, Easton C, Hickson M. Effects of Chlorhexidine mouthwash on the oral microbiome. Sci Rep. 2020 Mar 24;10(1):5254. doi: 10.1038/s41598-020-61912-4.
- Derived from this study: PubMed 41981946Mesa F, Rodriguez-Agurto A, Bonilla M, Rodriguez-Vilaboa D, Rodriguez-Vilaboa B, Bravo M. Betaine-, xylitol-, and extra virgin olive oil-based toothpaste modulates inflammation and oral nitric oxide pathway: Clinical trial in gingivitis. J Periodontol. 2026 Apr 14. doi: 10.1002/jper.70135. Online ahead of print.
- 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.
Francisco Luis Mesa Aguado principal investigator
Departamento de Estomatología, Facultad de Odontología
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Test composition Saliactive® (olive product, betaine and xylitol) in people with Oral Dysbiosis, run by Mucosa Innovations, S.L. at 1 site in Spain.
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 3 inclusion and 10 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 8 Jul 2024. 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 Spain. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Oral microbiota profile at baseline and after 4 months (time frame: 4 months). The study lists 6 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 NCT05463484, which also lists 6 linked publications.
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 8 Jul 2024.