Oral BiofilmPhase 4NCT03146390
Essential Oils With and Without Alcohol: Substantivity and Antiplaque Effect
A Phase 4 study testing Essential oils, Alcohol free essential oils and Water in people with Oral Biofilm and Dental Plaque, run by University of Santiago de Compostela at 1 site in Spain.
Trial summary
The Essential oils (EO) are composed by a wide diversity of products. Therefore, their antimicrobial activity will be related to their composition, configuration, amount and their possible interaction. Read more about this study
- Who is it for?
- Ages 20 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Oral Biofilm, Dental Plaque, Periodontitis
- What is being tested?
- Essential oils, Alcohol free essential oils and Water
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- 2 May 2017to 31 Aug 2017
- Phase
- Phase 4
- 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 20 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Systemically healthy adults.
- Minimum of 24 permanent teeth.
- No gingivitis (Community Periodontal Index score = 0).
- No periodontitis (Community Periodontal Index score = 0).
- Absence of untreated caries.
Who cannot join
- Smoker or former smoker.
- Presence of dental prostheses.
- Presence of orthodontic devices.
- Antibiotic treatment or routine use of oral antiseptics in the previous 3 months.
- Presence of any systemic disease that could alter the production or composition of saliva.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
University of Santiago de Compostela
Santiago de Compostela, A Coruña, 15782
Inmaculada Tomás, Senior Lecturer, +34981560031 ext. 1234, victor.quintas@usc.es
About this study
Official title: Essential Oils With and Without Alcohol: in Vivo Antibacterial Effect
The Essential oils (EO) are composed by a wide diversity of products. Therefore, their antimicrobial activity will be related to their composition, configuration, amount and their possible interaction. The traditional formulation containing EO (T-EO) is a complex mixture of phenolic compounds combined with determinate EO: 0.092% of eucalyptol, 0.064% of thymol, 0.06% of methyl-salicylate and y 0.042% of menthol. All of this solved in a hydroalcoholic vehicle containing from a 21.6% to a 26.9% of alcohol. Thus, T-EO contain ethanol, which is a chemical compound used in order to dissolve and stabilize the numerous substances present in the rinse. The concentration of ethanol present in the T-EO rinses, as previously said, is more than 20%. This concentration of ethanol, higher than 20%, is been found sufficient to dissolve the EO but insufficient to have a direct antibacterial effect. In fact, the manufacturer presents the alcohol contain (21.6%), among others, as an inactive ingredient in its formula. Over the years, the adequacy of the use of ethanol in mouthwashes, as well as their effects on the surfaces of composite restorations and their possible role in development of oropharyngeal cancer have been discussed. Although a direct cause-and-effect correlation between the development of oropharyngeal carcinoma and the use of alcohol-based rinses has not been demonstrated and probably it will never be (at least by epidemiological studies), it is considered desirable to eliminate ethanol from daily mouthwashes, especially for those patients at higher risk. Furthermore, the fact that the alcohol is present in its formula, have produced that some clinical practitioners do not prescribe the traditional formula due to the controversy of the issue. All this have lead to the development of new, alcohol free formulations of EO (Af-EO).
The composition of the Af-EO is exactly the same in their active ingredients (Eucalyptol, Thymol, Methyl-salycilate and Menthol), but sodium fluoride has been added. Some differences are found in their inactive ingredients. These are based on the alcohol containing of the T-EO, without presence in the Af-EO and the presence of Propylene Glycol, sodium lauryl sulfate and sucralose in the Af-EO, without presence in the T-EO.
Read more
In order to measure the efficacy of a mouthwash against the dental plaque two different concepts should be defined: the substantivity and antiplaque effect. The substantivity of an oral antiseptic is defined as the prolonged adherence to the oral surfaces and its slow release at effective doses which guarantee the persistence of the antimicrobial activity. The more substantivity an oral antiseptic has the better. For its study in vivo, the most popular models are those which analyze the effect that a single mouthwash has in a mature biofilm.
The second aspect that should be studied from an oral antiseptic, the antiplaque effect, is defined as the capacity that an agent has to avoid the formation of bacterial aggregates (plaque) on the oral surfaces. For its study in vivo, models start from a baseline sample with levels of plaque near to 0 in order to assess the power of the antiseptic to reduce the formation of bacterial plaque (normally dental plaque) against the control. A clinical study of 6 months using a determinate antiplaque agent is necessary in order to tag an antiseptic as effective. However, in the literature, there is an established model of 4 days of plaque regrowing which can assess the inhibitory activity that the mouthwashes have per se; furthermore, it determines the relative efficacy of the different formulations being considered as predictable of the antiplaque effect of an antiseptic.
In addition, another important factor in the study in vivo of an oral antiseptic is the necessity to conserve intact the oral biofilm at all stages: formation, recollection and analysis of the oral samples. This is in order not to interfere the delicate three dimensional structure of the oral biofilm which has been proven to be essential in the resistance to the effects of an external antiseptic agent. For these reasons, the study of the oral biofilm with the help of intraoral disks hold in specially designed apparatus combined with the application of the Confocal Laser Scanning Microscopy have proved to be very valuable at the study of the oral biofilm in its intact hydrated natural state.
Since an alcohol free formulation of the EO have come up to the market, it seems convenient to compare its effects to the traditional one. Although some studies comparing the effects of T-EO and Af-EO have been found, none of them assessed and compared their substantivity and antiplaque effect in an in vivo model of structured oral biofilm. For this reason, the aim of the present study was to compare the in vivo antibacterial effect (immediate effect, substantivity and antiplaque effect) of the EO with and without alcohol in structured oral biofilm.
- Conditions
- Oral Biofilm, Dental Plaque, Periodontitis
- Being tested
- Essential oils, Alcohol free essential oils, Water
- Keywords
- biofilms, essential oils, microscopy, confocal, mouthwashes
- Medical subject headings
- Dental Plaque, Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Essential oilsDrug
Also called Listerine Mentol
all subjects will perform all interventions of all arms
Alcohol free essential oilsDrug
Also called Listerine Zero
all subjects will perform all interventions of all arms
WaterOther
Also called Sterile Water
all subjects will perform all interventions of all arms
| Study group | Role | What they receive |
|---|---|---|
| Essential oils (Listerine Mentol) | Active comparator | 1. a single mouthwash with 20 ml of essential oils for 30 seconds
2. 20 ml rinses for 30 seconds with essential oils/2 times daily (1/0/1). Receives: Drug: Essential oils |
| Water | Placebo comparator | 1. a single mouthwash with 20 ml of sterile water for 30 seconds
2. 20 ml rinses for 30 seconds with sterile water/2 times daily (1/0/1). Receives: Other: Water |
| Alcohol free essential oils | Experimental | 1. a single mouthwash with 20 ml of alcohol free essential oils for 30 seconds
2. 20 ml rinses for 30 seconds with alcohol free essential oils/2 times daily (1/0/1). Receives: Drug: Alcohol free essential oils |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Bacterial viability (%) (substantivity)
ratio of alive/dead bacteria
Measured: Baseline, 30 seconds, 1 hour, 3 hours, 5 hours and 7 hours after the single application
Bacterial viability (%) (antiplaque effect)
ratio of alive/dead bacteria
Measured: 10 hours after the last mouthwash
Change in the Biofilm Thickness (Microns) (substantivity)
thickness of the biofilm from the base of the substrate to the top surface of the biofilm
Measured: baseline, 30 seconds, 1 hour, 3 hours, 5 hours and 7 hours after the single application
Biofilm Thickness (Microns) (Antiplaque effect)
thickness of the biofilm from the base of the substrate to the top surface of the biofilm
Measured: 10 hours after the last mouthwash
Covering Grade (%) (antiplaque effect)
area of the substrate that is covered by the biofilm after the 4 days of treatment
Measured: 10 hours after the last mouthwash
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start2 May 2017
- Primary completion31 Jul 2017 (estimated)
- Study completion31 Aug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oral BiofilmStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Santiago de Compostela
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Inmaculada Tomas, University of Santiago de Compostela
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03146390
- Sponsor's protocol ID
- 023/2017
- Status last verified
- May 2017
- First submitted
- 30 Apr 2017
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Quintas V, Prada-Lopez I, Donos N, Suarez-Quintanilla D, Tomas I. Antiplaque effect of essential oils and 0.2% chlorhexidine on an in situ model of oral biofilm growth: a randomised clinical trial. PLoS One. 2015 Feb 17;10(2):e0117177. doi: 10.1371/journal.pone.0117177. eCollection 2015.
PubMed 25689859Quintas V, Prada-Lopez I, Prados-Frutos JC, Tomas I. In situ antimicrobial activity on oral biofilm: essential oils vs. 0.2 % chlorhexidine. Clin Oral Investig. 2015 Jan;19(1):97-107. doi: 10.1007/s00784-014-1224-3. Epub 2014 Apr 1.
PubMed 24687247
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Essential Oils With and Without Alcohol: in Vivo Antibacterial Effect
- ClinicalTrials.gov ID
- NCT03146390
- Acronym / sponsor ID
- 023/2017
- Conditions
- Oral Biofilm, Dental Plaque, Periodontitis
- Keywords
- biofilms, essential oils, microscopy, confocal, mouthwashes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Santiago de CompostelaUniversity, hospital or other
- Study start
- 2 May 2017 (actual)
- Primary completion
- 31 Jul 2017 (estimated)
- Study completion
- 31 Aug 2017 (estimated)
- First posted
- 9 May 2017 (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 Essential oils (EO) are composed by a wide diversity of products. Therefore, their antimicrobial activity will be related to their composition, configuration, amount and their possible interaction. The traditional formulation containing EO (T-EO) is a complex mixture of phenolic compounds combined with determinate EO: 0.092% of eucalyptol, 0.064% of thymol, 0.06% of methyl-salicylate and y 0.042% of menthol. All of this solved in a hydroalcoholic vehicle containing from a 21.6% to a 26.9% of alcohol. Thus, T-EO contain ethanol, which is a chemical compound used in order to dissolve and stabilize the numerous substances present in the rinse. The concentration of ethanol present in the T-EO rinses, as previously said, is more than 20%. This concentration of ethanol, higher than 20%, is been found sufficient to dissolve the EO but insufficient to have a direct antibacterial effect. In fact, the manufacturer presents the alcohol contain (21.6%), among others, as an inactive ingredient in its formula. Over the years, the adequacy of the use of ethanol in mouthwashes, as well as their effects on the surfaces of composite restorations and their possible role in development of oropharyngeal cancer have been discussed. Although a direct cause-and-effect correlation between the development of oropharyngeal carcinoma and the use of alcohol-based rinses has not been demonstrated and probably it will never be (at least by epidemiological studies), it is considered desirable to eliminate ethanol from daily mouthwashes, especially for those patients at higher risk. Furthermore, the fact that the alcohol is present in its formula, have produced that some clinical practitioners do not prescribe the traditional formula due to the controversy of the issue. All this have lead to the development of new, alcohol free formulations of EO (Af-EO).
The composition of the Af-EO is exactly the same in their active ingredients (Eucalyptol, Thymol, Methyl-salycilate and Menthol), but sodium fluoride has been added. Some differences are found in their inactive ingredients. These are based on the alcohol containing of the T-EO, without presence in the Af-EO and the presence of Propylene Glycol, sodium lauryl sulfate and sucralose in the Af-EO, without presence in the T-EO.
In order to measure the efficacy of a mouthwash against the dental plaque two different concepts should be defined: the substantivity and antiplaque effect. The substantivity of an oral antiseptic is defined as the prolonged adherence to the oral surfaces and its slow release at effective doses which guarantee the persistence of the antimicrobial activity. The more substantivity an oral antiseptic has the better. For its study in vivo, the most popular models are those which analyze the effect that a single mouthwash has in a mature biofilm.
The second aspect that should be studied from an oral antiseptic, the antiplaque effect, is defined as the capacity that an agent has to avoid the formation of bacterial aggregates (plaque) on the oral surfaces. For its study in vivo, models start from a baseline sample with levels of plaque near to 0 in order to assess the power of the antiseptic to reduce the formation of bacterial plaque (normally dental plaque) against the control. A clinical study of 6 months using a determinate antiplaque agent is necessary in order to tag an antiseptic as effective. However, in the literature, there is an established model of 4 days of plaque regrowing which can assess the inhibitory activity that the mouthwashes have per se; furthermore, it determines the relative efficacy of the different formulations being considered as predictable of the antiplaque effect of an antiseptic.
In addition, another important factor in the study in vivo of an oral antiseptic is the necessity to conserve intact the oral biofilm at all stages: formation, recollection and analysis of the oral samples. This is in order not to interfere the delicate three dimensional structure of the oral biofilm which has been proven to be essential in the resistance to the effects of an external antiseptic agent. For these reasons, the study of the oral biofilm with the help of intraoral disks hold in specially designed apparatus combined with the application of the Confocal Laser Scanning Microscopy have proved to be very valuable at the study of the oral biofilm in its intact hydrated natural state.
Since an alcohol free formulation of the EO have come up to the market, it seems convenient to compare its effects to the traditional one. Although some studies comparing the effects of T-EO and Af-EO have been found, none of them assessed and compared their substantivity and antiplaque effect in an in vivo model of structured oral biofilm. For this reason, the aim of the present study was to compare the in vivo antibacterial effect (immediate effect, substantivity and antiplaque effect) of the EO with and without alcohol in structured oral biofilm.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Essential oils (Listerine Mentol) | Active comparator | Drug: Essential oils1. a single mouthwash with 20 ml of essential oils for 30 seconds 2. 20 ml rinses for 30 seconds with essential oils/2 times daily (1/0/1). |
| Water | Placebo comparator | Other: Water1. a single mouthwash with 20 ml of sterile water for 30 seconds 2. 20 ml rinses for 30 seconds with sterile water/2 times daily (1/0/1). |
| Alcohol free essential oils | Experimental | Drug: Alcohol free essential oils1. a single mouthwash with 20 ml of alcohol free essential oils for 30 seconds 2. 20 ml rinses for 30 seconds with alcohol free essential oils/2 times daily (1/0/1). |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Systemically healthy adults.
- Minimum of 24 permanent teeth.
- No gingivitis (Community Periodontal Index score = 0).
- No periodontitis (Community Periodontal Index score = 0).
- Absence of untreated caries.
Key exclusion criteria (5 listed)
- Smoker or former smoker.
- Presence of dental prostheses.
- Presence of orthodontic devices.
- Antibiotic treatment or routine use of oral antiseptics in the previous 3 months.
- Presence of any systemic disease that could alter the production or composition of saliva.
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 |
|---|---|---|
| Essential oilsAlso: Listerine Mentolall subjects will perform all interventions of all arms | Drug | Essential oils (Listerine Mentol) |
| Alcohol free essential oilsAlso: Listerine Zeroall subjects will perform all interventions of all arms | Drug | Alcohol free essential oils |
| WaterAlso: Sterile Waterall subjects will perform all interventions of all arms | Other | Water |
Primary outcome
Change in the Bacterial viability (%) (substantivity)
Time frame: Baseline, 30 seconds, 1 hour, 3 hours, 5 hours and 7 hours after the single application
ratio of alive/dead bacteria
Bacterial viability (%) (antiplaque effect)
Time frame: 10 hours after the last mouthwash
ratio of alive/dead bacteria
Change in the Biofilm Thickness (Microns) (substantivity)
Time frame: baseline, 30 seconds, 1 hour, 3 hours, 5 hours and 7 hours after the single application
thickness of the biofilm from the base of the substrate to the top surface of the biofilm
Biofilm Thickness (Microns) (Antiplaque effect)
Time frame: 10 hours after the last mouthwash
thickness of the biofilm from the base of the substrate to the top surface of the biofilm
Covering Grade (%) (antiplaque effect)
Time frame: 10 hours after the last mouthwash
area of the substrate that is covered by the biofilm after the 4 days of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Background: PubMed 25689859Quintas V, Prada-Lopez I, Donos N, Suarez-Quintanilla D, Tomas I. Antiplaque effect of essential oils and 0.2% chlorhexidine on an in situ model of oral biofilm growth: a randomised clinical trial. PLoS One. 2015 Feb 17;10(2):e0117177. doi: 10.1371/journal.pone.0117177. eCollection 2015.
- Background: PubMed 24687247Quintas V, Prada-Lopez I, Prados-Frutos JC, Tomas I. In situ antimicrobial activity on oral biofilm: essential oils vs. 0.2 % chlorhexidine. Clin Oral Investig. 2015 Jan;19(1):97-107. doi: 10.1007/s00784-014-1224-3. Epub 2014 Apr 1.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Essential oils, Alcohol free essential oils and Water in people with Oral Biofilm and Dental Plaque, run by University of Santiago de Compostela 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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 9 May 2017. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Inmaculada Tomás, Senior Lecturer (+34981560031 ext. 12344, victor.quintas@usc.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Bacterial viability (%) (substantivity) (time frame: Baseline, 30 seconds, 1 hour, 3 hours, 5 hours and 7 hours after the single application). The study lists 5 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 NCT03146390, which also lists 2 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 9 May 2017.