HalitosisPhase 4NCT02789436
Effect of Probiotic Lozenges on Halitosis in Patients With Chronic Periodontitis
A Phase 4 study testing L. reuteri Prodentis® lozenges in people with Halitosis, run by University of Zagreb at 1 site in Croatia.
Trial summary
The purpose of this study is to determine whether Lactobacillus reuteri-containing lozenges (Prodentis) are effective in treatment of halitosis in patients with chronic periodontitis. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Halitosis
- What is being tested?
- L. reuteri Prodentis® lozenges
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteCroatia
- Study dates
- Jun 2016to Sep 2016
- 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients, above age of 30
- Non-smokers or ex-smokers (not smoking in the past year)
- Moderate to advanced untreated chronic periodontitis
- Good compliance and following of oral hygiene instructions
- Halitosis in active phase and patient's subjective complaint
- Informed consent by the patient
Who cannot join
- Aggressive periodontitis
- Antibiotics administered up to 3 months prior to this study
- Pregnancy and breastfeeding
- Immunosuppressive therapy
- Oral neoplasms (including radiation or chemotherapy)
- Diabetes mellitus
Show all 9Show fewer
- Acute oral inflammation or infection
- Poor, unsatisfactory oral hygiene and lack of compliance
- Use of dietary supplements containing probiotics within 2 weeks prior to study start
Trial locations and contacts
1 site in 1 country.
Larisa Musić, DMD contact
Croatia1 site
University of Zagreb, School of Dental Medicine Zagreb
Zagreb, 10000
Larisa Musić, DMD, lmusic@sfzg.hr
About this study
Official title: Effect of Probiotic Lactobacillus Reuteri-containing Lozenges (Prodentis) on Halitosis in Patients With Chronic Periodontitis
The purpose of this study is to determine whether Lactobacillus reuteri-containing lozenges (Prodentis) are effective in treatment of halitosis in patients with chronic periodontitis.
Read the detailed description
Bad breath (oral malodor, lat. halitosis) is amongst most common patients' complaints in the dental office. Ironically, available literature and research done on this topic thus far are relatively scarce. Oral malodor is most commonly caused by oral bacteria (87%), yet it can also be sourced from ear, nose and throat region and in a small percentage from distant parts of the body or is of unknown origin. Periodontal pathogens and other Gram(-) anaerobic microorganisms such as Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Enterobacter cloacae, Prevotella loescheii and Porphyromonas endodontalis are regarded as producers of malodorous gases. Namely, these bacterial species and periodontal pathogens particularly produce so called volatile sulfur compounds (VSC) which give mouth air its malodorness. Methylmercaptan, hydrogen sulfide and dimethyl sulfide are waste products of bacterial metabolism, specifically degradation of sulfur-, methionine- and cysteine-containing aminoacids. Offensive smells also stem from other compounds which do not contain sulfur, diamines and polyamines such as cadaverine, putrescine and skatole.
Probiotics are defined as living microorganisms which are considered to have beneficial health effect on their host when consumed in adequate amount. Regarding their advantageous role in periodontal disease, inhibition of specific periodontal pathogens and alteration of host immune response through multifactorial causes are thought to be their main working mechanisms. Reuterin and reutericyclin are two bacteriocins produced by Lactobacillus reuteri that inhibit growth of pathogenic bacteria, while bacterium also exhibits strong capacity of host tissue adherence and subsequent competition with pathogens.
Based on this data, research on efficacy of probiotic lozenges on halitosis in patients with chronic periodontitis.
- Conditions
- Halitosis
- Being tested
- L. reuteri Prodentis® lozenges, Placebo lozenges
- Keywords
- halitosis, chronic periodontitis, probiotic
- Medical subject headings
- Halitosis, Chronic Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L. reuteri Prodentis® lozengesDrug
Twice daily, for 28 days
Placebo lozengesOther
Twice daily, for 28 days
| Study group | Role | What they receive |
|---|---|---|
| L. reuteri Prodentis® lozenges | Experimental | 15 subjects
Probiotic lozenges used in the trial is a non-commercial product provided by BioGaia AB, Lund, Sweden. The Probiotic lozenges consist of a minimum of 200 million live L. reuteri (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 (L. reuteri Prodentis®). Probiotic lozenges are used twice daily for 28 days. Receives: Drug: L. reuteri Prodentis® lozenges |
| Placebo lozenges | Placebo comparator | 15 subjects
Placebo lozenges used in the trial is non-commercial product provided by BioGaia AB, Lund, Sweden.Placebo lozenges are taken twice daily for 28 days. Receives: Other: Placebo lozenges |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in VSC concentration in mouth air
Assessed with halimeter
Measured: 28 days
Secondary outcomes (3)
Changes in halitosis associated quality of life
Assessed with Halitosis Associated Life-quality Test (Kizhnev et al., 2011)
Measured: 28 days
Change from Baseline in Plaque Accumulation (PCR)
Assessed with PCR index (Plaque Control Record - O'Leary et al., 1972)
Measured: 28 days
Change from Baseline in Bleeding on Probing (BOP)
Assessed with BOP index (Bleeding on Probing, Ainamo and Bay, 1975)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionSep 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)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 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
- Collaborators
- BioGaia AB
- Responsible party
- Principal investigator, Larisa Musić, University of Zagreb
- Investigators
- Darije Plančak, Professor, Study director, University of Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789436
- Sponsor's protocol ID
- 05-PA-26-10/15
- Status last verified
- May 2016
- First submitted
- 4 Apr 2016
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Loesche WJ, Kazor C. Microbiology and treatment of halitosis. Periodontol 2000. 2002;28:256-79. doi: 10.1034/j.1600-0757.2002.280111.x.
PubMed 12013345Delanghe G, Ghyselen J, van Steenberghe D, Feenstra L. Multidisciplinary breath-odour clinic. Lancet. 1997 Jul 19;350(9072):187. doi: 10.1016/S0140-6736(05)62354-9. No abstract available.
PubMed 9250193Persson S, Claesson R, Carlsson J. The capacity of subgingival microbiotas to produce volatile sulfur compounds in human serum. Oral Microbiol Immunol. 1989 Sep;4(3):169-72. doi: 10.1111/j.1399-302x.1989.tb00246.x.
PubMed 2639302Persson S, Edlund MB, Claesson R, Carlsson J. The formation of hydrogen sulfide and methyl mercaptan by oral bacteria. Oral Microbiol Immunol. 1990 Aug;5(4):195-201. doi: 10.1111/j.1399-302x.1990.tb00645.x.
PubMed 2082242Goldberg S, Kozlovsky A, Gordon D, Gelernter I, Sintov A, Rosenberg M. Cadaverine as a putative component of oral malodor. J Dent Res. 1994 Jun;73(6):1168-72. doi: 10.1177/00220345940730060701.
PubMed 8046106Walker WA. Mechanisms of action of probiotics. Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S87-91; discussion S144-51. doi: 10.1086/523335.
PubMed 18181730Haukioja A. Probiotics and oral health. Eur J Dent. 2010 Jul;4(3):348-55.
PubMed 20613927
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotic Lactobacillus Reuteri-containing Lozenges (Prodentis) on Halitosis in Patients With Chronic Periodontitis
- ClinicalTrials.gov ID
- NCT02789436
- Acronym / sponsor ID
- 05-PA-26-10/15
- Conditions
- Halitosis
- Keywords
- halitosis, chronic periodontitis, probiotic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Collaborators
- BioGaia AB
- Study start
- Jun 2016
- Primary completion
- Sep 2016 (estimated)
- First posted
- 3 Jun 2016 (estimated)
- 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 purpose of this study is to determine whether Lactobacillus reuteri-containing lozenges (Prodentis) are effective in treatment of halitosis in patients with chronic periodontitis.
Detailed description
Bad breath (oral malodor, lat. halitosis) is amongst most common patients' complaints in the dental office. Ironically, available literature and research done on this topic thus far are relatively scarce. Oral malodor is most commonly caused by oral bacteria (87%), yet it can also be sourced from ear, nose and throat region and in a small percentage from distant parts of the body or is of unknown origin. Periodontal pathogens and other Gram(-) anaerobic microorganisms such as Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum, Enterobacter cloacae, Prevotella loescheii and Porphyromonas endodontalis are regarded as producers of malodorous gases. Namely, these bacterial species and periodontal pathogens particularly produce so called volatile sulfur compounds (VSC) which give mouth air its malodorness. Methylmercaptan, hydrogen sulfide and dimethyl sulfide are waste products of bacterial metabolism, specifically degradation of sulfur-, methionine- and cysteine-containing aminoacids. Offensive smells also stem from other compounds which do not contain sulfur, diamines and polyamines such as cadaverine, putrescine and skatole.
Probiotics are defined as living microorganisms which are considered to have beneficial health effect on their host when consumed in adequate amount. Regarding their advantageous role in periodontal disease, inhibition of specific periodontal pathogens and alteration of host immune response through multifactorial causes are thought to be their main working mechanisms. Reuterin and reutericyclin are two bacteriocins produced by Lactobacillus reuteri that inhibit growth of pathogenic bacteria, while bacterium also exhibits strong capacity of host tissue adherence and subsequent competition with pathogens.
Based on this data, research on efficacy of probiotic lozenges on halitosis in patients with chronic periodontitis.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L. reuteri Prodentis® lozenges | Experimental | Drug: L. reuteri Prodentis® lozenges15 subjects Probiotic lozenges used in the trial is a non-commercial product provided by BioGaia AB, Lund, Sweden. The Probiotic lozenges consist of a minimum of 200 million live L. reuteri (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 (L. reuteri Prodentis®). Probiotic lozenges are used twice daily for 28 days. |
| Placebo lozenges | Placebo comparator | Other: Placebo lozenges15 subjects Placebo lozenges used in the trial is non-commercial product provided by BioGaia AB, Lund, Sweden.Placebo lozenges are taken twice daily for 28 days. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients, above age of 30
- Non-smokers or ex-smokers (not smoking in the past year)
- Moderate to advanced untreated chronic periodontitis
- Good compliance and following of oral hygiene instructions
- Halitosis in active phase and patient's subjective complaint
Key exclusion criteria (9 listed)
- Aggressive periodontitis
- Antibiotics administered up to 3 months prior to this study
- Pregnancy and breastfeeding
- Immunosuppressive therapy
- Oral neoplasms (including radiation or chemotherapy)
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 |
|---|---|---|
| L. reuteri Prodentis® lozengesTwice daily, for 28 days | Drug | L. reuteri Prodentis® lozenges |
| Placebo lozengesTwice daily, for 28 days | Other | Placebo lozenges |
Primary outcome
Change in VSC concentration in mouth air
Time frame: 28 days
Assessed with halimeter
3 secondary outcomes
Changes in halitosis associated quality of life
Time frame: 28 days
Change from Baseline in Plaque Accumulation (PCR)
Time frame: 28 days
Change from Baseline in Bleeding on Probing (BOP)
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2016.
- Background: PubMed 12013345Loesche WJ, Kazor C. Microbiology and treatment of halitosis. Periodontol 2000. 2002;28:256-79. doi: 10.1034/j.1600-0757.2002.280111.x.
- Background: PubMed 9250193Delanghe G, Ghyselen J, van Steenberghe D, Feenstra L. Multidisciplinary breath-odour clinic. Lancet. 1997 Jul 19;350(9072):187. doi: 10.1016/S0140-6736(05)62354-9. No abstract available.
- Background: PubMed 2639302Persson S, Claesson R, Carlsson J. The capacity of subgingival microbiotas to produce volatile sulfur compounds in human serum. Oral Microbiol Immunol. 1989 Sep;4(3):169-72. doi: 10.1111/j.1399-302x.1989.tb00246.x.
- Background: PubMed 2082242Persson S, Edlund MB, Claesson R, Carlsson J. The formation of hydrogen sulfide and methyl mercaptan by oral bacteria. Oral Microbiol Immunol. 1990 Aug;5(4):195-201. doi: 10.1111/j.1399-302x.1990.tb00645.x.
- Background: PubMed 8046106Goldberg S, Kozlovsky A, Gordon D, Gelernter I, Sintov A, Rosenberg M. Cadaverine as a putative component of oral malodor. J Dent Res. 1994 Jun;73(6):1168-72. doi: 10.1177/00220345940730060701.
- Background: PubMed 18181730Walker WA. Mechanisms of action of probiotics. Clin Infect Dis. 2008 Feb 1;46 Suppl 2:S87-91; discussion S144-51. doi: 10.1086/523335.
- Background: PubMed 20613927Haukioja A. Probiotics and oral health. Eur J Dent. 2010 Jul;4(3):348-55.
- 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.
Larisa Musić, DMD contact
Darije Plančak, Professor study director
University of Zagreb
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 L. reuteri Prodentis® lozenges in people with Halitosis, run by University of Zagreb at 1 site in Croatia.
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 6 inclusion and 9 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 3 Jun 2016. 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 Croatia. 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 Larisa Musić, DMD (lmusic@sfzg.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in VSC concentration in mouth air (time frame: 28 days). 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 NCT02789436, which also lists 7 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 3 Jun 2016.