Chronic PeriodontitisPhase 2HAMELDENTNCT03656484
New Periodontitis Treatment Based on Hyaluronic Acid and Melatonin
A Phase 2 study testing Tetracycline-Metronidazole (TM) group and TM-Melatonin-Hyaluronic acid (TM-MHa) group in people with Chronic Periodontitis, run by Concordia Dent Srl at 2 sites in Romania.
Trial summary
The aim of the present study is to determine whether the association of Melatonin and Hyaluronic Acid to the antimicrobial TM paste (3% Tetracyclin and 3% Metronidazole) for periodontal maintenance therapy can improve the attachment level (AL) and alveolar bone support for moderate chronic periodontitis. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Chronic Periodontitis
- What is being tested?
- Tetracycline-Metronidazole (TM) group and TM-Melatonin-Hyaluronic acid (TM-MHa) group
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesRomania
- Study dates
- 15 Jan 2019to 20 Dec 2019
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- moderate chronic periodontitis, that is, > 2 interproximal sites with AL > 4 mm (not on the same tooth), or > 2 interproximal sites with pocket depth (PD) > 5 mm (not on the same tooth) (1),
- at least 20 teeth present in the mouth,
- no periodontal therapy during the last 6 months,
- no antibiotic during the last 6 months,
- good general health (no systemic condition affecting the course of periodontal disease, including malignancy), pregnancy,
- no allergy to the product components,
- good mental health.
Who cannot join
- Patients not willing to sign consent form.
- Patients not agreeing with the treatment protocol.
Trial locations and contacts
2 sites in 1 country.
Romania2 sites
Concordia Dent Clinic
Bucharest, 041335
"Carol Davila"University of Medicine and Pharmacy
Bucharest
About this study
Official title: Innovative Technology for Assessing the Periodontal Disease and New Periodontitis Treatment Based on Hyaluronic Acid and Melatonin
The aim of the present study is to determine whether the association of Melatonin and Hyaluronic Acid to the antimicrobial TM paste (3% Tetracyclin and 3% Metronidazole) for periodontal maintenance therapy can improve the attachment level (AL) and alveolar bone support for moderate chronic periodontitis.
Read the detailed description
Local drug delivery agents in periodontology has gained acceptance and popularity compared to systemic drugs due to decreased risk in development of resistant flora, opportunist infection, and side effects.
In order to improve the topical treatment for chronic periodontitis, Melatonin and Hyaluronic Acid have been added to antimicrobial topic paste commercially available.
- A complex matrix composed of Tetracycline, Metronidazole, Melatonin and Hyaluronic Acid have been developed for local treatment of chronic periodontitis.
- Microbiological, physical, chemical characterization of the newly obtained matrix and biocompatibility tests have been performed.
- A randomized clinical trial will be perform on 50 patients with moderate chronic periodontitis recruited based on eligibility criteria and informed consent signed.
- Mechanical debridement of the pockets by scaling and root planning will be performed prior to the adjunctive therapy.
- Extensive clinical examination including charting the remaining teeth, clinical attachment level (CAL), presence of dental plaque (PI), gingival index (GI), calculus (CI), bleeding on probing (BOP), radiographic assessment and identification of periodontal pathogens with micro-IDent® test will be performed at the beginning of the study and 6 month after its completion.
- Each patient will be randomized using sealed envelopes (according to a computer-generated randomization list) to one of the following topical administration (in the periodontal pocket of affected teeth), for 30 consecutive days: Tetracycline and Metronidazole paste (TM), n=25 patients and Tetracycline, Metronidazole, Melatonin, Hyaluronic Acid paste (TM-MHa), n=25 patients.
- A statistical evaluation of data recorded during the entire follow-up period will be performed.
- Conditions
- Chronic Periodontitis
- Being tested
- Tetracycline-Metronidazole (TM) group, TM-Melatonin-Hyaluronic acid (TM-MHa) group
- Keywords
- Melatonin, Hyaluronic Acid, Tetracycline, Metronidazole, topic paste, chronic periodontitis
- Medical subject headings
- Chronic Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetracycline-Metronidazole (TM) groupDrug
Also called TM group
Following mechanical debridement (scaling and root planning) the above-mentioned paste will be topically administrated in the periodontal pocket of affected teeth once a day, for 30 consecutive days.
TM-Melatonin-Hyaluronic acid (TM-MHa) groupDrug
Also called TM-MHa group
Following mechanical debridement (scaling and root planning) the above-mentioned paste will be topically administrated in the periodontal pocket of affected teeth once a day, for 30 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Tetracycline-Metronidazole (TM) group | Active comparator | Topical administration (in the periodontal pocket of affected teeth), for 30 consecutive days of 3%Tetracycline and 3%Metronidazole paste (TM), n=25 patients, considered control group. Receives: Drug: Tetracycline-Metronidazole (TM) group |
| TM-Melatonin-Hyaluronic acid (TM-MHa) group | Experimental | Topical administration (in the periodontal pocket of affected teeth), for 30 consecutive days of 3% Tetracycline, 3% Metronidazole, 0.18% Melatonin and 3% Hyaluronic Acid (TM-MHa) paste, n=25 patients, considered experimental group. Receives: Drug: TM-Melatonin-Hyaluronic acid (TM-MHa) group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Clinical attachment level (CAL)
Changes CAL from Baseline (before treatment) at 6 months will be assessed using a standardised protocol.
Measured: before treatment (Baseline), at 6 months post treatment completion
Secondary outcomes (2)
Changes in Alveolar bone height
Changes in the alveolar bone height from Baseline (before treatment) at 6 months will be assessed using standardised Radiographic measurements.
Measured: before treatment (Baseline), at 6 months post treatment completion
Treatment's influence on bactrial pathogens
Periodontal pathogens will be identified by performing micro-IDent® assay before treatment (Baseline) and 6 month after its completion. Micro-IDent® test uses chain polymerisation reaction, with colorimetric detection, to identify the following pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Treponema denticola.
Measured: before treatment (Baseline), at 6 months post treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2018
- Study start15 Jan 2019
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Chronic PeriodontitisStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Concordia Dent Srl
- Sponsor type
- University, hospital or other
- Collaborators
- Carol Davila University of Medicine and Pharmacy, Romanian National Authority for Scientific Research and Innovation (UEFISCIDI), University Politechnica of Bucharest, TURKEY MEDISEN Ltd
- Responsible party
- Principal investigator, Corina Marilena Cristache, Carol Davila University of Medicine and Pharmacy
- Investigators
- CORINA MARILENA CRISTACHE, Principal investigator, Carol Davila University of Medicine and Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03656484
- Sponsor's protocol ID
- CCDI-UEFISCDI 39/2018
- Acronym
- HAMELDENT
- Status last verified
- Jan 2020
- First submitted
- 29 Aug 2018
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ. Update of the case definitions for population-based surveillance of periodontitis. J Periodontol. 2012 Dec;83(12):1449-54. doi: 10.1902/jop.2012.110664. Epub 2012 Mar 16.
PubMed 22420873Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075.
PubMed 25494600Matesanz-Perez P, Garcia-Gargallo M, Figuero E, Bascones-Martinez A, Sanz M, Herrera D. A systematic review on the effects of local antimicrobials as adjuncts to subgingival debridement, compared with subgingival debridement alone, in the treatment of chronic periodontitis. J Clin Periodontol. 2013 Mar;40(3):227-41. doi: 10.1111/jcpe.12026. Epub 2013 Jan 16.
PubMed 23320860Jepsen K, Jepsen S. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 2000. 2016 Jun;71(1):82-112. doi: 10.1111/prd.12121.
PubMed 27045432Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002 Jul;17(7):1219-29. doi: 10.1359/jbmr.2002.17.7.1219.
PubMed 12096835Montero J, Lopez-Valverde N, Ferrera MJ, Lopez-Valverde A. Changes in crevicular cytokines after application of melatonin in patients with periodontal disease. J Clin Exp Dent. 2017 Sep 1;9(9):e1081-e1087. doi: 10.4317/jced.53934. eCollection 2017 Sep.
PubMed 29075409Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5.
PubMed 26692007Diker N, Gulsever S, Koroglu T, Yilmaz Akcay E, Oguz Y. Effects of Hyaluronic Acid and Hydroxyapatite/Beta-tricalcium Phosphate in Combination on Bone Regeneration of a Critical-size Defect in an Experimental Model. J Craniofac Surg. 2018 Jun;29(4):1087-1093. doi: 10.1097/SCS.0000000000004338.
PubMed 29438204Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW. Bacteriostatic effects of hyaluronic acid. J Periodontol. 1999 Apr;70(4):370-4. doi: 10.1902/jop.1999.70.4.370.
PubMed 10328647Sakai A, Akifusa S, Itano N, Kimata K, Kawamura T, Koseki T, Takehara T, Nishihara T. Potential role of high molecular weight hyaluronan in the anti-Candida activity of human oral epithelial cells. Med Mycol. 2007 Feb;45(1):73-9. doi: 10.1080/13693780601039607.
PubMed 17325947
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Innovative Technology for Assessing the Periodontal Disease and New Periodontitis Treatment Based on Hyaluronic Acid and Melatonin
- ClinicalTrials.gov ID
- NCT03656484
- Acronym / sponsor ID
- HAMELDENT / CCDI-UEFISCDI 39/2018
- Conditions
- Chronic Periodontitis
- Keywords
- Melatonin, Hyaluronic Acid, Tetracycline, Metronidazole, topic paste, chronic periodontitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Concordia Dent SrlUniversity, hospital or other
- Collaborators
- Carol Davila University of Medicine and Pharmacy, Romanian National Authority for Scientific Research and Innovation (UEFISCIDI), University Politechnica of Bucharest, TURKEY MEDISEN Ltd
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 4 Sep 2018 (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 aim of the present study is to determine whether the association of Melatonin and Hyaluronic Acid to the antimicrobial TM paste (3% Tetracyclin and 3% Metronidazole) for periodontal maintenance therapy can improve the attachment level (AL) and alveolar bone support for moderate chronic periodontitis.
Detailed description
Local drug delivery agents in periodontology has gained acceptance and popularity compared to systemic drugs due to decreased risk in development of resistant flora, opportunist infection, and side effects.
In order to improve the topical treatment for chronic periodontitis, Melatonin and Hyaluronic Acid have been added to antimicrobial topic paste commercially available.
- A complex matrix composed of Tetracycline, Metronidazole, Melatonin and Hyaluronic Acid have been developed for local treatment of chronic periodontitis.
- Microbiological, physical, chemical characterization of the newly obtained matrix and biocompatibility tests have been performed.
- A randomized clinical trial will be perform on 50 patients with moderate chronic periodontitis recruited based on eligibility criteria and informed consent signed.
- Mechanical debridement of the pockets by scaling and root planning will be performed prior to the adjunctive therapy.
- Extensive clinical examination including charting the remaining teeth, clinical attachment level (CAL), presence of dental plaque (PI), gingival index (GI), calculus (CI), bleeding on probing (BOP), radiographic assessment and identification of periodontal pathogens with micro-IDent® test will be performed at the beginning of the study and 6 month after its completion.
- Each patient will be randomized using sealed envelopes (according to a computer-generated randomization list) to one of the following topical administration (in the periodontal pocket of affected teeth), for 30 consecutive days: Tetracycline and Metronidazole paste (TM), n=25 patients and Tetracycline, Metronidazole, Melatonin, Hyaluronic Acid paste (TM-MHa), n=25 patients.
- A statistical evaluation of data recorded during the entire follow-up period will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tetracycline-Metronidazole (TM) group | Active comparator | Drug: Tetracycline-Metronidazole (TM) groupTopical administration (in the periodontal pocket of affected teeth), for 30 consecutive days of 3%Tetracycline and 3%Metronidazole paste (TM), n=25 patients, considered control group. |
| TM-Melatonin-Hyaluronic acid (TM-MHa) group | Experimental | Drug: TM-Melatonin-Hyaluronic acid (TM-MHa) groupTopical administration (in the periodontal pocket of affected teeth), for 30 consecutive days of 3% Tetracycline, 3% Metronidazole, 0.18% Melatonin and 3% Hyaluronic Acid (TM-MHa) paste, n=25 patients, considered experimental group. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- moderate chronic periodontitis, that is, > 2 interproximal sites with AL > 4 mm (not on the same tooth), or > 2 interproximal sites with pocket depth (PD) > 5 mm (not on the same tooth) (1),
- at least 20 teeth present in the mouth,
- no periodontal therapy during the last 6 months,
- no antibiotic during the last 6 months,
- good general health (no systemic condition affecting the course of periodontal disease, including malignancy), pregnancy,
Key exclusion criteria (2 listed)
- Patients not willing to sign consent form.
- Patients not agreeing with the treatment protocol.
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 |
|---|---|---|
| Tetracycline-Metronidazole (TM) groupAlso: TM groupFollowing mechanical debridement (scaling and root planning) the above-mentioned paste will be topically administrated in the periodontal pocket of affected teeth once a day, for 30 consecutive days. | Drug | Tetracycline-Metronidazole (TM) group |
| TM-Melatonin-Hyaluronic acid (TM-MHa) groupAlso: TM-MHa groupFollowing mechanical debridement (scaling and root planning) the above-mentioned paste will be topically administrated in the periodontal pocket of affected teeth once a day, for 30 consecutive days. | Drug | TM-Melatonin-Hyaluronic acid (TM-MHa) group |
Primary outcome
Changes in Clinical attachment level (CAL)
Time frame: before treatment (Baseline), at 6 months post treatment completion
Changes CAL from Baseline (before treatment) at 6 months will be assessed using a standardised protocol.
2 secondary outcomes
Changes in Alveolar bone height
Time frame: before treatment (Baseline), at 6 months post treatment completion
Treatment's influence on bactrial pathogens
Time frame: before treatment (Baseline), at 6 months post treatment completion
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 27 Jan 2020.
- Background: PubMed 22420873Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ. Update of the case definitions for population-based surveillance of periodontitis. J Periodontol. 2012 Dec;83(12):1449-54. doi: 10.1902/jop.2012.110664. Epub 2012 Mar 16.
- Background: PubMed 25494600Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075.
- Background: PubMed 23320860Matesanz-Perez P, Garcia-Gargallo M, Figuero E, Bascones-Martinez A, Sanz M, Herrera D. A systematic review on the effects of local antimicrobials as adjuncts to subgingival debridement, compared with subgingival debridement alone, in the treatment of chronic periodontitis. J Clin Periodontol. 2013 Mar;40(3):227-41. doi: 10.1111/jcpe.12026. Epub 2013 Jan 16.
- Background: PubMed 27045432Jepsen K, Jepsen S. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 2000. 2016 Jun;71(1):82-112. doi: 10.1111/prd.12121.
- Background: PubMed 12096835Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res. 2002 Jul;17(7):1219-29. doi: 10.1359/jbmr.2002.17.7.1219.
- Background: PubMed 29075409Montero J, Lopez-Valverde N, Ferrera MJ, Lopez-Valverde A. Changes in crevicular cytokines after application of melatonin in patients with periodontal disease. J Clin Exp Dent. 2017 Sep 1;9(9):e1081-e1087. doi: 10.4317/jced.53934. eCollection 2017 Sep.
- Background: PubMed 26692007Andersen LP, Gogenur I, Rosenberg J, Reiter RJ. The Safety of Melatonin in Humans. Clin Drug Investig. 2016 Mar;36(3):169-75. doi: 10.1007/s40261-015-0368-5.
- Background: PubMed 29438204Diker N, Gulsever S, Koroglu T, Yilmaz Akcay E, Oguz Y. Effects of Hyaluronic Acid and Hydroxyapatite/Beta-tricalcium Phosphate in Combination on Bone Regeneration of a Critical-size Defect in an Experimental Model. J Craniofac Surg. 2018 Jun;29(4):1087-1093. doi: 10.1097/SCS.0000000000004338.
- Background: PubMed 10328647Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW. Bacteriostatic effects of hyaluronic acid. J Periodontol. 1999 Apr;70(4):370-4. doi: 10.1902/jop.1999.70.4.370.
- Background: PubMed 17325947Sakai A, Akifusa S, Itano N, Kimata K, Kawamura T, Koseki T, Takehara T, Nishihara T. Potential role of high molecular weight hyaluronan in the anti-Candida activity of human oral epithelial cells. Med Mycol. 2007 Feb;45(1):73-9. doi: 10.1080/13693780601039607.
- Individual participant dataSharing planned: No
Related trials for Chronic Periodontitis
Not yet recruiting
Clinical and Inflammatory Outcomes of Regenerative Endodontic Treatment Using Injectable Platelet-Rich Fibrin in Mature Necrotic Teeth With Chronic Apical Periodontitis.
Chronic Apical Periodontitis, Pulp Necrosis
Recruiting
Effect of Cyperus Articulatus on Bacterial Reduction and Postoperative Pain
Chronic Apical Periodontitis
RecruitingObservational study
Prevalence and Associated Factors of High BMI and Periodontitis in Thai Adults Aged Under 60 Years
Diabete Mellitus, Dyslipidaemia
RecruitingObservational study
Evaluation of Masticatory Performance in Patients With Periodontitis
Periodontitis, Adult, Periodontitis
Recruiting
Postoperative Pain and Success of Single-Visit Root Canal Treatment Using Different Root Canal Sealers in Asymptomatic Teeth
Single-visit, Periapical Periodontitis
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.
CORINA MARILENA CRISTACHE principal investigator
Carol Davila University of Medicine and Pharmacy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tetracycline-Metronidazole (TM) group and TM-Melatonin-Hyaluronic acid (TM-MHa) group in people with Chronic Periodontitis, run by Concordia Dent Srl at 2 sites in Romania.
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 7 inclusion and 2 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 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Romania. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Changes in Clinical attachment level (CAL) (time frame: before treatment (Baseline), at 6 months post treatment completion). 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 NCT03656484, which also lists 10 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 27 Jan 2020.