HalitosisPhase 1NCT06583720
Comparative Study Between Photodynamic Therapy with LED Associated with Probiotics in the Treatment of Halitosis
A Phase 1 study testing Oral hygiene at home, aPDT and Probiotics in people with Halitosis, run by University of Nove de Julho at 1 site in Brazil.
Trial summary
Halitosis is a term that defines any odor or bad smell coming from the oral cavity, which can have a local or systemic origin. This project aims to verify if there is a difference in the effectiveness of treatment with antimicrobial photodynamic therapy (aPDT) with LED associated with treatment using probiotics in… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Halitosis
- What is being tested?
- Oral hygiene at home, aPDT and Probiotics
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Nov 2024to 30 Dec 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of halitosis showing sulfhydride (SH2) ≥ 112 ppb in gas chromatography.
Who cannot join
- Individuals with dentofacial anomalies (such as cleft lip, cleft palate and nasopalatine);
- Undergoing orthodontic and/or orthopedic treatment;
- Undergoing oncological treatment;
- With systemic alterations (gastrointestinal, renal, hepatic)
- Undergoing antibiotic treatment up to 1 month before the research;
- Pregnant women.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Nove de Julho University
São Paulo, São Paulo, 01525-000
Sandra K Bussadori, PhD, +55 11 2633-9000, sandra.skb@gmail.com
About this study
Official title: Comparative Study Between Photodynamic Therapy with LED Associated with Probiotics in the Treatment of Halitosis - Controlled Randomized Clinical Trial
Halitosis is a term that defines any odor or bad smell coming from the oral cavity, which can have a local or systemic origin. This project aims to verify if there is a difference in the effectiveness of treatment with antimicrobial photodynamic therapy (aPDT) with LED associated with treatment using probiotics in reducing halitosis. 92 participants, aged 18 to 60 years, diagnosed with halitosis, presenting sulfhydride (SH2) ≥ 112 ppb in gas chromatography will be selected. Participants will be randomly divided into 4 groups (n=23), which will receive different treatments: Group 1 (control): brushing, dental floss and tongue scraper; Group 2: brushing, dental floss, tongue scraper and aPDT with blue LED and annatto; Group 3: brushing, dental flossing, tongue scraper and aPDT with blue LED, annatto and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®); Group 4: brushing, dental flossing, tongue scraper and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). The results of the halimetry will be compared before, immediately after the treatments, thirty days after and sixty days after. The microbiological analysis will be performed by counting the colony forming unit of viable bacteria in the tongue coating at these same times. The microbiome analysis will be performed before, thirty days after and sixty days after the treatments after DNA extraction. All groups will be treated with oral hygiene instructions with a toothbrush, toothpaste and dental floss as well as receiving material for this practice. The normality of the data will be measured by the Shapiro-Wilk test, and in the case of normality the Analysis of Variance (ANOVA) test will be applied, and in the case of non-parametric data, the Kruskal-Wallis test will be used. The Wilcoxon test will be used to analyze the results of each treatment in the two study periods.
- Conditions
- Halitosis
- Being tested
- Oral hygiene at home, aPDT, Probiotics
- Medical subject headings
- Halitosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral hygiene at homeProcedure or surgery
Participant will be taught on how to correctly brush their teeth, use dental floss and scrape their tongues at home.
aPDTProcedure or surgery
A weekly aPDT session will be performed for a period of 30 days, with the photosensitizer (PS) annatto manipulated at a concentration of 20% (Fórmula e Ação®). 2 ml (quantity measured with a pipette) will be applied to the middle third and dorsum of the tongue for 2 minutes for incubation (pre-irradiation time). The excess will be removed with a suction device in order to keep the surface moist with the PS itself. Six points will be irradiated with a distance of 1 cm between them, considering the light scattering halo; the LED will be positioned at a distance from the tongue so as to form a 2 cm halo at each point. The device will be previously calibrated with a wavelength of 395-480 nm, for 20 seconds per point, energy of 9.6 J.
ProbioticsDietary supplement
Probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®) (OralBiotic; Master Products, Fort Lauderdale, Florida, United States) will be used. Each patient will receive 60 lozenges, which should be allowed to dissolve slowly and completely in the mouth. Patients are instructed to use the lozenges twice a day for a period of 30 days.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Experimental | Participants in this group will perform brushing, dental floss and tongue scraper. Receives: Procedure: Oral hygiene at home |
| aPDT group | Experimental | Participants in this group will receive brushing, dental floss, tongue scraper and aPDT with blue LED and annatto. Receives: Procedure: Oral hygiene at home; Procedure: aPDT |
| aPDT and Probiotics group | Experimental | Participants in this group will receive brushing, dental floss, lingual scraper and aPDT with blue LED, annatto and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). Receives: Procedure: Oral hygiene at home; Procedure: aPDT; Dietary Supplement: Probiotics |
| Probiotics group | Experimental | Participants in this group will receive brushing, dental floss, lingual scraper and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). Receives: Procedure: Oral hygiene at home; Dietary Supplement: Probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Halimetry Levels
The collection of oral air will follow the manufacturer\'s instructions (Oral ChromaTM Manual Instruction), where the participant will be instructed to rinse with cysteine (10 mM) for 1 minute, then keep their mouth closed for another minute. A syringe from the same manufacturer, suitable for collecting oral air, will be placed in the patient\'s mouth. For 1 minute, the patient will remain with their mouth closed, breathing through their nose, without touching the syringe with their tongue. The plunger will be pulled out, we will empty the air from the syringe into the patient\'s mouth again and pull the plunger again to fill the syringe with the breath sample. We will clean the tip of the syringe with gauze to remove moisture from the saliva, place the gas injection needle on the syringe, and adjust the plunger to 0.5 ml. The collected gases are injected into the inlet port of the device with a single movement.
Measured: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
Secondary outcomes (2)
Changes in Microbiological Analysis
The samples will be collected with a swab on the back of the tongue, then placed in an eppendorf containing BHI (Brain Heart Infusion) serving as a transport medium, for later cultivation of these samples to be able to detect the total number of viable bacteria. Initially, the samples will be homogenized for 30 seconds in a Vortex apparatus, and then diluted in the order of 10-1 to 10-5 in a 96-well microtiter plate containing 180 microliters of PBS in each well. We take 20 microliters of each sample and follow the dilution sequence. After the dilution is performed, we will take 5 aliquots of 10 microliters of this suspension and they will be seeded in a petri dish with blood agar. The cultures will then be incubated for 72 hours at 37°C in an atmosphere of 85% nitrogen (N2), 10% carbon dioxide (CO2) and 5% hydrogen (H2), achieved through the use of an anaerobic generation system. This will provide visual access to the total number of viable bacteria in colony forming units (CFU).
Measured: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
Changes in Microbiome Analysis
Tongue coating samples will be collected from the posterior third of the tongue using a sterile swab and deposited in 1.5 mL centrifuge tubes containing Tris-EDTA buffer (10 mM Tris-HCL, 0.1 mM EDTA, pH 7.5) and stored at -80 °C. After thawing, the samples will be vortexed for one minute. DNA extraction will be performed using the Master Pure DNA Extraction Kit (Epicentre Technologies Corp., Chicago, IL, USA) according to the manufacturer\'s instructions. The purified DNA will be resuspended in TE buffer. The microbiome and variations between communities will be analyzed using pyrosequencing and 16S rRNA gene metagenomics methods.
Measured: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2024
- Study start1 Nov 2024
- Primary completion30 Nov 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
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 HalitosisStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nove de Julho
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sandra Kalil Bussadori, University of Nove de Julho
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06583720
- Sponsor's protocol ID
- HaliFAPESP
- Status last verified
- Mar 2025
- First submitted
- 1 Sep 2024
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be added to OSF.
Publications
Mandetta ARH, Gallo JMAS, Ribeiro CDPV, Goncalves MLL, Sobral APT, Motta LJ, Horliana ACRT, Mesquita-Ferrari RA, Rodriguez VS, Prates RA, Duran CCG, Fernandes KPS, Bussadori SK. Comparative study of photodynamic therapy with LED and probiotics in the treatment of halitosis: protocol for a randomised controlled clinical trial. BMJ Open. 2025 Apr 25;15(4):e095544. doi: 10.1136/bmjopen-2024-095544.
PubMed 40280606
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study Between Photodynamic Therapy with LED Associated with Probiotics in the Treatment of Halitosis - Controlled Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06583720
- Acronym / sponsor ID
- HaliFAPESP
- Conditions
- Halitosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- University of Nove de JulhoUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 4 Sep 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.
Halitosis is a term that defines any odor or bad smell coming from the oral cavity, which can have a local or systemic origin. This project aims to verify if there is a difference in the effectiveness of treatment with antimicrobial photodynamic therapy (aPDT) with LED associated with treatment using probiotics in reducing halitosis. 92 participants, aged 18 to 60 years, diagnosed with halitosis, presenting sulfhydride (SH2) ≥ 112 ppb in gas chromatography will be selected. Participants will be randomly divided into 4 groups (n=23), which will receive different treatments: Group 1 (control): brushing, dental floss and tongue scraper; Group 2: brushing, dental floss, tongue scraper and aPDT with blue LED and annatto; Group 3: brushing, dental flossing, tongue scraper and aPDT with blue LED, annatto and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®); Group 4: brushing, dental flossing, tongue scraper and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). The results of the halimetry will be compared before, immediately after the treatments, thirty days after and sixty days after. The microbiological analysis will be performed by counting the colony forming unit of viable bacteria in the tongue coating at these same times. The microbiome analysis will be performed before, thirty days after and sixty days after the treatments after DNA extraction. All groups will be treated with oral hygiene instructions with a toothbrush, toothpaste and dental floss as well as receiving material for this practice. The normality of the data will be measured by the Shapiro-Wilk test, and in the case of normality the Analysis of Variance (ANOVA) test will be applied, and in the case of non-parametric data, the Kruskal-Wallis test will be used. The Wilcoxon test will be used to analyze the results of each treatment in the two study periods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control group | Experimental | Procedure: Oral hygiene at homeParticipants in this group will perform brushing, dental floss and tongue scraper. |
| aPDT group | Experimental | Procedure: Oral hygiene at home, Procedure: aPDTParticipants in this group will receive brushing, dental floss, tongue scraper and aPDT with blue LED and annatto. |
| aPDT and Probiotics group | Experimental | Procedure: Oral hygiene at home, Procedure: aPDT, Dietary Supplement: ProbioticsParticipants in this group will receive brushing, dental floss, lingual scraper and aPDT with blue LED, annatto and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). |
| Probiotics group | Experimental | Procedure: Oral hygiene at home, Dietary Supplement: ProbioticsParticipants in this group will receive brushing, dental floss, lingual scraper and probiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Diagnosis of halitosis showing sulfhydride (SH2) ≥ 112 ppb in gas chromatography.
Key exclusion criteria (6 listed)
- Individuals with dentofacial anomalies (such as cleft lip, cleft palate and nasopalatine);
- Undergoing orthodontic and/or orthopedic treatment;
- Undergoing oncological treatment;
- With systemic alterations (gastrointestinal, renal, hepatic)
- Undergoing antibiotic treatment up to 1 month before the research;
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 hygiene at homeParticipant will be taught on how to correctly brush their teeth, use dental floss and scrape their tongues at home. | Procedure or surgery | Control group, Probiotics group, aPDT and Probiotics group, aPDT group |
| aPDTA weekly aPDT session will be performed for a period of 30 days, with the photosensitizer (PS) annatto manipulated at a concentration of 20% (Fórmula e Ação®). 2 ml (quantity measured with a pipette) will be applied to the middle third and dorsum of the tongue for 2 minutes for incubation (pre-irradiation time). The excess will be removed with a suction device in order to keep the surface moist with the PS itself. Six points will be irradiated with a distance of 1 cm between them, considering the light scattering halo; the LED will be positioned at a distance from the tongue so as to form a 2 cm halo at each point. The device will be previously calibrated with a wavelength of 395-480 nm, for 20 seconds per point, energy of 9.6 J. | Procedure or surgery | aPDT and Probiotics group, aPDT group |
| ProbioticsProbiotic lozenges containing Streptococcus salivarius K12 (BLIS K12®) (OralBiotic; Master Products, Fort Lauderdale, Florida, United States) will be used. Each patient will receive 60 lozenges, which should be allowed to dissolve slowly and completely in the mouth. Patients are instructed to use the lozenges twice a day for a period of 30 days. | Dietary supplement | Probiotics group, aPDT and Probiotics group |
Primary outcome
Changes in Halimetry Levels
Time frame: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
The collection of oral air will follow the manufacturer\'s instructions (Oral ChromaTM Manual Instruction), where the participant will be instructed to rinse with cysteine (10 mM) for 1 minute, then keep their mouth closed for another minute. A syringe from the same manufacturer, suitable for collecting oral air, will be placed in the patient\'s mouth. For 1 minute, the patient will remain with their mouth closed, breathing through their nose, without touching the syringe with their tongue. The plunger will be pulled out, we will empty the air from the syringe into the patient\'s mouth again and pull the plunger again to fill the syringe with the breath sample. We will clean the tip of the syringe with gauze to remove moisture from the saliva, place the gas injection needle on the syringe, and adjust the plunger to 0.5 ml. The collected gases are injected into the inlet port of the device with a single movement.
2 secondary outcomes
Changes in Microbiological Analysis
Time frame: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
Changes in Microbiome Analysis
Time frame: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Derived from this study: PubMed 40280606Mandetta ARH, Gallo JMAS, Ribeiro CDPV, Goncalves MLL, Sobral APT, Motta LJ, Horliana ACRT, Mesquita-Ferrari RA, Rodriguez VS, Prates RA, Duran CCG, Fernandes KPS, Bussadori SK. Comparative study of photodynamic therapy with LED and probiotics in the treatment of halitosis: protocol for a randomised controlled clinical trial. BMJ Open. 2025 Apr 25;15(4):e095544. doi: 10.1136/bmjopen-2024-095544.
- Individual participant dataSharing planned: Yes. Data will be added to OSF.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oral hygiene at home, aPDT and Probiotics in people with Halitosis, run by University of Nove de Julho at 1 site in Brazil.
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 1 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 30 Mar 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 Brazil. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sandra K Bussadori (+55 11 2633-9000, pesquisa@uninove.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Halimetry Levels (time frame: Baseline, immediately after treatment, 30 days after treatment and 60 days after treatment.). 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 NCT06583720, 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 30 Mar 2025.