Healthy Adult ParticipantsEarly Phase 1NCT07592416
Clinical, Microbiological and Immunological Effects of the Adjuvant Use of Systemic Antibiotics and Probiotics in the Non-surgical Treatment of Periodontitis
A Early Phase 1 study testing Amoxicilin and Metronidazole and Probiotic Therapy in people with Healthy Adult Participants and Periodontal Disease, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
Although robust evidence supports the benefits of antibiotics in periodontal treatment, the potential adverse effects of this therapy cannot be overlooked. These include concerns regarding the emergence of antimicrobial resistance and the non-ecological impact of antimicrobials on the gut microbiome, which may be… Read more about this study
- Who is it for?
- Ages 30 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Participants, Periodontal Disease
- What is being tested?
- Amoxicilin and Metronidazole and Probiotic Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteBrazil
- Study dates
- 22 Aug 2023to 11 Feb 2026
- Phase
- Early Phase 1
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults with a diagnosis of generalized periodontitis, defined as involvement of ≥30% of teeth, classified as: Stage III or Stage IV, and Grade B or Grade C, according to the 2018 classification.
- Presence of at least one tooth with ≥1 interproximal site exhibiting: Probing depth (PD) ≥6 mm, and Clinical attachment loss (CAL) ≥5 mm.
- Presence of at least 15 teeth, excluding third molars and teeth indicated for extraction.
- Presence of at least 6 non contiguous teeth, each with ≥1 interproximal site presenting PD and CAL ≥5 mm.
Who cannot join
- Current smokers or former smokers who quit less than 5 years prior to enrollment.
- Pregnant or breastfeeding women.
- History of periodontal treatment within the previous 6 months.
- Continuous use of oral antiseptics within the last 6 months.
- Use of systemic antibiotics, corticosteroids, non steroidal anti inflammatory drugs, immunosuppressants, estrogen, estrogen receptor modulators, or medications affecting bone metabolism (e.g., alendronate, calcitonin) within the last 6 months.
- Presence of systemic conditions that may alter the host response, including: Diabetes mellitus, HIV infection, Down syndrome.
Show all 9Show fewer
- Medical conditions requiring antibiotic prophylaxis for dental procedures (e.g., mitral valve prolapse).
- Known allergy or hypersensitivity to amoxicillin, metronidazole, penicillins, or related compounds.
- Use of probiotics within the last 6 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical, Microbiological and Immunological Effects of the Adjuvant Use of Systemic Antibiotics and Probiotics in the Non-surgical Treatment of Periodontitis: a Controlled and Randomized Clinical Trial
Although robust evidence supports the benefits of antibiotics in periodontal treatment, the potential adverse effects of this therapy cannot be overlooked. These include concerns regarding the emergence of antimicrobial resistance and the non-ecological impact of antimicrobials on the gut microbiome, which may be closely linked to the etiopathogenesis of periodontitis and to the maintenance of long-term periodontal treatment outcomes. In this context, probiotics may represent a promising alternative strategy to reduce the need for antibiotics, particularly in severe cases of periodontitis.
Read the detailed description
Scaling and root planing (SRP) is the most widely used treatment modality in periodontal therapy. However, a subset of periodontal sites does not respond adequately to this approach, and certain individuals exhibit susceptibility patterns that limit their response to initial treatment. Therefore, to overcome the limitations of SRP alone, adjunctive therapies-such as antibiotics and probiotics-may be employed.
The aim of this randomized, controlled, double-blind clinical trial is to evaluate the effects of adjunctive therapies (antibiotics and probiotics) associated with non-surgical periodontal therapy in individuals diagnosed with periodontitis stages III or IV, grades B or C. A total of sixty individuals with a clinical diagnosis of periodontitis will be treated with SRP alone or SRP combined with antibiotics or probiotics. Participants will be randomly allocated into three groups: Control (SRP), Test 1 (SRP + amoxicillin and metronidazole), and Test 2 (SRP + probiotics).
The adjunctive agents evaluated in this study will be a combination of systemic antibiotics (amoxicillin and metronidazole) and the probiotic Bifidobacterium animalis subsp. lactis HN019. Antibiotics will be administered for 14 days, three times daily, whereas probiotics will be administered for 90 days, twice daily. Adjunctive therapies will commence immediately after the first week of periodontal instrumentation.
Clinical follow-up will be conducted at baseline (pre-intervention), and at 3, 6, 9, and 12 months post-treatment. At baseline, 6 months, and 12 months, gingival crevicular fluid, subgingival biofilm, peripheral blood, and fecal samples will be collected, along with the assessment of periodontal clinical parameters. Levels of the cytokines IL-6, TNF-α, IFN-γ, IL-10, IL-1β, and IL-8 will be quantified in gingival crevicular fluid and peripheral blood samples using enzyme-linked immunosorbent assays.
Subgingival biofilm and fecal samples will be subjected to 16S ribosomal RNA gene amplification by PCR and sequenced using Illumina technology (MiSeq or MiniSeq; Illumina, San Diego, CA, USA). Sequencing data will be analyzed using reference databases of the human oral and intestinal microbiomes. Statistical analyses will be performed using an alpha level of 0.05 (p < 0.05).
- Conditions
- Healthy Adult Participants, Periodontal Disease
- Being tested
- Amoxicilin and Metronidazole, Probiotic Therapy
- Keywords
- periodontitis, periodontal disease, probiotics, antibiotics
- Medical subject headings
- Periodontal Diseases, Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amoxicilin and MetronidazoleDrug
Also called Amoxicilin, Metronidazole, Antibiotics
The antibiotic group will receive amoxicilin and metronidazole, the probiotic group will receive probiotics
Probiotic TherapyOther
Patients will receive probiotic lozenges as an adjuvant therapy to periodontal treatment.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | No intervention | Not described |
| Probiotic | Experimental | To compare the effects of probiotic as an adjuvant therapy Receives: Other: Probiotic Therapy |
| Antibiotic | Experimental | To compare the effects as an adjuvant therapy Receives: Drug: Amoxicilin and Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Periodontal Probing Depth (PD)
A full-mouth periodontal examination will be performed using a North Carolina periodontal probe (Hu-Friedy, Chicago, IL, USA). Probing depth (PD) will be measured in millimeters at six sites per tooth.
Measured: every 3 months, up to 1 year
Clinical Attachment Level (CAL)
Clinical attachment level (CAL) will be measured in millimeters at six sites per tooth using a North Carolina periodontal probe.
Measured: Every 3 months, up to 1 year
Bleeding on Probing (BOP)
Bleeding on probing will be assessed dichotomously (presence/absence) at six sites per tooth during full-mouth periodontal examination
Measured: Every 3 months, up to 1 year
Visible Supragingival Biofilm
Presence or absence of visible supragingival biofilm will be assessed on four tooth surfaces during full-mouth periodontal examination.
Measured: Every 3 months, up to 1 year
Distance from Cementoenamel Junction to Gingival Margin
The distance from the cementoenamel junction to the gingival margin will be measured in millimeters at six sites per tooth.
Measured: Every 3 months, up to 1 year
Suppuration
Suppuration will be assessed dichotomously (presence/absence) at six sites per tooth during periodontal examination.
Measured: Every 3 months, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2026
- Study start22 Aug 2023
- Primary completion30 Jan 2026
- Study completion11 Feb 2026
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 Healthy Adult ParticipantsStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participant allocation will be performed using a computer-generated random number table. The study coordinator will assign patients to one of three groups: Control (SRP), Test 1 (SRP + amoxicillin and metronidazole), and Test 2 (SRP + probiotic), with 20 participants in each group. Participants in Test 1 will receive the antibiotic combination three times daily for 14 days, while participants in Test 2 will receive two probiotic tablets daily for 90 days.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ademir Leite Filho, University of Sao Paulo
- Investigators
- Michel Reis Messora, PhD, Study director, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07592416
- Sponsor's protocol ID
- 75898223.7.0000.5419
- Status last verified
- May 2026
- First submitted
- 28 Apr 2026
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study protocol will be shared as a guide for further research.
Publications
Haas AN, Furlaneto F, Gaio EJ, Gomes SC, Palioto DB, Castilho RM, Sanz M, Messora MR. New tendencies in non-surgical periodontal therapy. Braz Oral Res. 2021 Sep 24;35(Supp 2):e095. doi: 10.1590/1807-3107bor-2021.vol35.0095. eCollection 2021.
PubMed 34586209
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Microbiological and Immunological Effects of the Adjuvant Use of Systemic Antibiotics and Probiotics in the Non-surgical Treatment of Periodontitis: a Controlled and Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07592416
- Acronym / sponsor ID
- 75898223.7.0000.5419
- Conditions
- Healthy Adult Participants, Periodontal Disease
- Keywords
- periodontitis, periodontal disease, probiotics, antibiotics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- 22 Aug 2023 (actual)
- Primary completion
- 30 Jan 2026 (actual)
- Study completion
- 11 Feb 2026 (actual)
- First posted
- 18 May 2026 (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.
Although robust evidence supports the benefits of antibiotics in periodontal treatment, the potential adverse effects of this therapy cannot be overlooked. These include concerns regarding the emergence of antimicrobial resistance and the non-ecological impact of antimicrobials on the gut microbiome, which may be closely linked to the etiopathogenesis of periodontitis and to the maintenance of long-term periodontal treatment outcomes. In this context, probiotics may represent a promising alternative strategy to reduce the need for antibiotics, particularly in severe cases of periodontitis.
Detailed description
Scaling and root planing (SRP) is the most widely used treatment modality in periodontal therapy. However, a subset of periodontal sites does not respond adequately to this approach, and certain individuals exhibit susceptibility patterns that limit their response to initial treatment. Therefore, to overcome the limitations of SRP alone, adjunctive therapies-such as antibiotics and probiotics-may be employed.
The aim of this randomized, controlled, double-blind clinical trial is to evaluate the effects of adjunctive therapies (antibiotics and probiotics) associated with non-surgical periodontal therapy in individuals diagnosed with periodontitis stages III or IV, grades B or C. A total of sixty individuals with a clinical diagnosis of periodontitis will be treated with SRP alone or SRP combined with antibiotics or probiotics. Participants will be randomly allocated into three groups: Control (SRP), Test 1 (SRP + amoxicillin and metronidazole), and Test 2 (SRP + probiotics).
The adjunctive agents evaluated in this study will be a combination of systemic antibiotics (amoxicillin and metronidazole) and the probiotic Bifidobacterium animalis subsp. lactis HN019. Antibiotics will be administered for 14 days, three times daily, whereas probiotics will be administered for 90 days, twice daily. Adjunctive therapies will commence immediately after the first week of periodontal instrumentation.
Clinical follow-up will be conducted at baseline (pre-intervention), and at 3, 6, 9, and 12 months post-treatment. At baseline, 6 months, and 12 months, gingival crevicular fluid, subgingival biofilm, peripheral blood, and fecal samples will be collected, along with the assessment of periodontal clinical parameters. Levels of the cytokines IL-6, TNF-α, IFN-γ, IL-10, IL-1β, and IL-8 will be quantified in gingival crevicular fluid and peripheral blood samples using enzyme-linked immunosorbent assays.
Subgingival biofilm and fecal samples will be subjected to 16S ribosomal RNA gene amplification by PCR and sequenced using Illumina technology (MiSeq or MiniSeq; Illumina, San Diego, CA, USA). Sequencing data will be analyzed using reference databases of the human oral and intestinal microbiomes. Statistical analyses will be performed using an alpha level of 0.05 (p < 0.05).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Participant allocation will be performed using a computer-generated random number table. The study coordinator will assign patients to one of three groups: Control (SRP), Test 1 (SRP + amoxicillin and metronidazole), and Test 2 (SRP + probiotic), with 20 participants in each group. Participants in Test 1 will receive the antibiotic combination three times daily for 14 days, while participants in Test 2 will receive two probiotic tablets daily for 90 days.
| Arm | Type | Receives |
|---|---|---|
| Placebo | No intervention | – |
| Probiotic | Experimental | Other: Probiotic TherapyTo compare the effects of probiotic as an adjuvant therapy |
| Antibiotic | Experimental | Drug: Amoxicilin and MetronidazoleTo compare the effects as an adjuvant therapy |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Adults with a diagnosis of generalized periodontitis, defined as involvement of ≥30% of teeth, classified as: Stage III or Stage IV, and Grade B or Grade C, according to the 2018 classification.
- Presence of at least one tooth with ≥1 interproximal site exhibiting: Probing depth (PD) ≥6 mm, and Clinical attachment loss (CAL) ≥5 mm.
- Presence of at least 15 teeth, excluding third molars and teeth indicated for extraction.
- Presence of at least 6 non contiguous teeth, each with ≥1 interproximal site presenting PD and CAL ≥5 mm.
Key exclusion criteria (9 listed)
- Current smokers or former smokers who quit less than 5 years prior to enrollment.
- Pregnant or breastfeeding women.
- History of periodontal treatment within the previous 6 months.
- Continuous use of oral antiseptics within the last 6 months.
- Use of systemic antibiotics, corticosteroids, non steroidal anti inflammatory drugs, immunosuppressants, estrogen, estrogen receptor modulators, or medications affecting bone metabolism (e.g., alendronate, calcitonin) within the last 6 months.
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 |
|---|---|---|
| Amoxicilin and MetronidazoleAlso: Amoxicilin, Metronidazole, AntibioticsThe antibiotic group will receive amoxicilin and metronidazole, the probiotic group will receive probiotics | Drug | Antibiotic |
| Probiotic TherapyPatients will receive probiotic lozenges as an adjuvant therapy to periodontal treatment. | Other | Probiotic |
Primary outcome
Periodontal Probing Depth (PD)
Time frame: every 3 months, up to 1 year
A full-mouth periodontal examination will be performed using a North Carolina periodontal probe (Hu-Friedy, Chicago, IL, USA). Probing depth (PD) will be measured in millimeters at six sites per tooth.
Clinical Attachment Level (CAL)
Time frame: Every 3 months, up to 1 year
Clinical attachment level (CAL) will be measured in millimeters at six sites per tooth using a North Carolina periodontal probe.
Bleeding on Probing (BOP)
Time frame: Every 3 months, up to 1 year
Bleeding on probing will be assessed dichotomously (presence/absence) at six sites per tooth during full-mouth periodontal examination
Visible Supragingival Biofilm
Time frame: Every 3 months, up to 1 year
Presence or absence of visible supragingival biofilm will be assessed on four tooth surfaces during full-mouth periodontal examination.
Distance from Cementoenamel Junction to Gingival Margin
Time frame: Every 3 months, up to 1 year
The distance from the cementoenamel junction to the gingival margin will be measured in millimeters at six sites per tooth.
Suppuration
Time frame: Every 3 months, up to 1 year
Suppuration will be assessed dichotomously (presence/absence) at six sites per tooth during periodontal examination.
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 18 May 2026.
- Background: PubMed 34586209Haas AN, Furlaneto F, Gaio EJ, Gomes SC, Palioto DB, Castilho RM, Sanz M, Messora MR. New tendencies in non-surgical periodontal therapy. Braz Oral Res. 2021 Sep 24;35(Supp 2):e095. doi: 10.1590/1807-3107bor-2021.vol35.0095. eCollection 2021.
- Individual participant dataSharing planned: Yes. The study protocol will be shared as a guide for further research.
Related trials for Healthy Adult Participants
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruiting
REM Enhancement Sleep Technology for Well-being, Emotion, and Life Lift
Healthy Adult Participants
RecruitingPhase 1
A Study to Learn How Different Forms of the Study Medicine Called Berobenatide is Taken up Into the Blood in Adults With Overweight or Obesity
Overweight and/or Obesity, Healthy Participants
RecruitingObservational study
Magnetic Field Maps With NV Application Kit MCG
Technical Feasibility and Performance of the Sensor System, Healthy Adult
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.
Michel Reis Messora, PhD study director
University of Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Amoxicilin and Metronidazole and Probiotic Therapy in people with Healthy Adult Participants and Periodontal Disease, run by University of Sao Paulo 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 4 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: finished, as of the sponsor's last update on 18 May 2026. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Periodontal Probing Depth (PD) (time frame: every 3 months, up to 1 year). 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 NCT07592416, 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 18 May 2026.