Caries; EnamelPhase 2IMUNODENTNCT03334461
Immunological and Regenerative Implications of Corrosion of Dental Materials
A Phase 2 study testing Exposure to oral antiseptics or enamel remineralisation agent in people with Caries; Enamel and Gingivitis, run by University of Rijeka at 1 site in Croatia.
Trial summary
During orthodontic treatment intraoral corrosion results with release of nickel and titanium ions from orthodontic appliances in surrounding tissues. Those transported in the saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Caries; Enamel, Gingivitis
- What is being tested?
- Exposure to oral antiseptics or enamel remineralisation agent
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteCroatia
- Study dates
- 1 Dec 2015to 17 May 2022
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- patients with fixed orthodontic appliances
- must be able to do a mouthwash
Who cannot join
- patients allergic to fluoride agents and chlorhexidine gluconate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Immunological and Regenerative Implications of Corrosion of Dental Materials in Children and Adolescents
During orthodontic treatment intraoral corrosion results with release of nickel and titanium ions from orthodontic appliances in surrounding tissues. Those transported in the saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Nickel is one of the strongest contact allergens, present in numerous dental alloys. The aim of this project is to investigate the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistance of gingivitis to therapy, and bacterial resistance to antibiotics) and changes in performance of orthodontic appliances with repercussion on regeneration of bone and periodontal tissues.
Read the detailed description
Tooth movement with appliances based on nickel and titanium has got great osteogenic potential and can regenerate deficient parts of alveolar bone and gingiva and rehabilitate compromised occlusal relations and a patient's masticatory function. Due to the extended duration of this therapy, different procedures are carried out and materials are applied for prevention and regeneration of damaged enamel and oral mucosa. The oral cavity may be considered a galvanic cell in which dental alloys act as electrodes, while saliva and oral preventive and regenerative agents act as electrolites. The interaction causes corrosion, reduction of elasticity and increase of stiffness of appliances, which may in turn result in excessive forces, a disruption of tissue regeneration and irreparable damage of tooth roots, surrounding alveolar bone, periodontal ligament, gingiva and pulp.
During the extended exposion, released corrosive products in surrounding tissues and those transported in saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Today, allergies are ever more frequent and arise earlier in life. A specific group are children and young adolescents in pubertal growth, a period in which the immune system develops. Nickel is one of the strongest contact allergens, present in numerous dental alloys. Nickel allergy is occurs in up to 28.5% of population and cannot be deemed as low potential risk anymore.
In contrast, titan was considered a biocompatible material of no allergic potential. However, there is an increase in the frequency of presentations of different hypersensitivity reactions to titan, especially in patients with pacemakers. Numerous patients with hip endoprostheses, stents, dental implans and orthodontic appliances are exposed to titan. Titan allergy may be the cause of unexplained cases of failure and rejection of dental implants. Nickel and titan could cause bacterial resistance to antibiotics which may complicate treatment of a series of infections that are more frequent in children and adolescents.
Regulations for safety of medical products regulate safety issues of materials through mandatory laboratory testing and expertise. However, the testing of interactions of these materials with newly formed materials for prevention of damage and regeneration of orodental tissues is not obligatory prior to the start of their commercial use. Such testing should be conducted by independent scientific insitutions and not by producers with direct commercial interest.
The aim of this project is to investigate:
- the corrosion of dental materials and appliances based on nickel and titan (in saliva and due to interaction with probiotics, remineralising agents and antiseptics)
- the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistency of gingivitis to therapy, and bacterial resistance to antibiotics)
- the effect of nickel and titan ions cellular level
- changes in performance of dental appliances with repercussion on regeneration of bone and periodontal tissues.
- Conditions
- Caries; Enamel, Gingivitis
- Being tested
- Exposure to oral antiseptics or enamel remineralisation agent
- Keywords
- Oral antiseptics, remineralisation agents
- Medical subject headings
- Gingivitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure to oral antiseptics or enamel remineralisation agentCombination product
| Study group | Role | What they receive |
|---|---|---|
| high concentration enamel remineralisation agent | Experimental | first month brushing teeth three times per day: twice per day with high-fluorides gel (Mirafluor K gel cola 6150 ppm F pH 5.1) and once per day without toothpaste and fluoride gel next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) Receives: Combination Product: Exposure to oral antiseptics or enamel remineralisation agent |
| oral antiseptic | Experimental | first month brushing teeth without toothpaste three times per day and using oral antiseptic chlorhexidine mouthwash (Curasept ADS 212 a 200ml 0,12%) twice per day next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) Receives: Combination Product: Exposure to oral antiseptics or enamel remineralisation agent |
| Control | No intervention | regular oral hygiene without exposure to oral antiseptic or high concentration enamel remineralisation agent three months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reaction of oral bacterial flora to oral antiseptics and dental remineralisation agents
Detection of change of count of Streptococcus mutans, sorbinus and salivarius and total bacterial count assesed by qPCR in the dental plaque before and after intervention in patients with fixed orthodontic appliances.
Measured: 30 days
Secondary outcomes (11)
Dental arch shape
Measuring anterior and posterior dental arch width (in millimeters), anterior depth and depth to width ratio in orthodontic patients wearing uncoated nickel-titanium 0.020''x0.020'' archwire on the day of putting the archwire and on the day of removing it.
Measured: 90 days
Oral hygiene
Assessing accumulation of dental biofilm with Modified Silness and Loe Plaque Index (0-3; 0=no plaque and 3=continuous line of dental bacterial plaque more than 1 millimetre).
Measured: 210 days
pH of dental biofilm
Measuring pH of dental biofilm (colorimetric test with pH scale range from 4 to 7).
Measured: 210 days
Gingivitis
Assessing extent of gingivitis by Full Mouth Bleeding Score (percentage).
Measured: 210 days
Corrosion of dental alloy
Potential of corrosion, passive film breakdown and repassivation (mV)
Measured: 90 days
Surface roughness of dental alloy
Surface roughness assessed by Atomic Force Microscopy (nm)
Measured: 90 days
Friction of dental alloy
Friction coefficient (no units)
Measured: 90 days
Forces produced by dental alloy
Load and unload forces measured by three-point bend test (N)
Measured: 90 days
Hardness of dental alloy
Vickers Pyramid Number (HV)
Measured: 90 days
Stifness of dental alloy
Young's modulus and yield strength (GPa)
Measured: 90 days
Elasticity of dental alloy
Modulus of resilience and springback ratio (MJ/m-3)
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start1 Dec 2015
- Primary completion30 Mar 2022
- Study completion17 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Caries; EnamelStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trail
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rijeka
- Sponsor type
- University, hospital or other
- Collaborators
- Croatian Science Foundation
- Responsible party
- Principal investigator, Stjepan Spalj, University of Rijeka
- Investigators
- Stjepan Spalj, PhD, Principal investigator, University of medicine Rijeka
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334461
- Sponsor's protocol ID
- IP-2014-09-7500
- Acronym
- IMUNODENT
- Status last verified
- May 2022
- First submitted
- 30 Oct 2017
- Last updated
- 26 May 2022
- Results posted
- No
- Individual data sharing
- No
Publications
Belasic TZ, Pejova B, Curkovic HO, Kamenar E, Cetenovic B, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Angle Orthod. 2021 Jul 1;91(4):528-537. doi: 10.2319/052620-480.1.
PubMed 33566077Zibar Belasic T, Zigante M, Perkovic V, Uhac M, Spalj S. Comparison of dental and periodontal condition of patients unexposed and exposed to metal orthodontic appliance. Book of Abstracts of the 7th international Congress of School of Dental Medicine University of Zagreb, Rovinj, Croatia, 21.-22.05.2021. Acta Stomatol Croat. 2021;55:213-6.
Zibar Belasic T, Zigante M, Uhac M, Karlovic S, Jelovica Badovinac I, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on biomechanics of remodeling of dental arches. 8th Virtual World Congress of Dental Students - Abstract book. Zagreb, Croatia, 2020. p. 2.
Cindric L, Mohar Vitezić B, Zigante M, Spalj S, Markova Car E. Changes of bacterial profile of dental biofilm during orthodontic treatment and influence of fluorides and chlorhexidine. South Eur J Orthod Dentofac Res. Conference proceedings - 1st Congress of the Faculty of Dental medicine, University of Rijeka, Croatia, October 1st-3rd 2020. Rijeka, Hrvatska, 2020. p. 55.
Zibar Belasic T, Pejova B, Otmacic Curkovic H, Kamenar E, Cetenovic B, Spalj S. Intraoral application of antiseptics and fluorides during orthodontic treatment does not affect significantly corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Prvi kongres Fakulteta dentalne medicine Sveučilišta u Rijeci, Rijeka, 1-2.10.2020. Knjiga sažetaka. South Eur J Orthod Dentofac Res 2020;7:56.
Zibar Belasic T, Mohar Vitezic B, Zigante M, Spalj S, Markova Car E. Supragingival biofilm composition changes during orthodontic treatment and chlorhexidine use. Book of Abstracts 97th Annual Congress of the European Orthodontic Society, Limassol, Cipar, 30.05.-03.06.2022.
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunological and Regenerative Implications of Corrosion of Dental Materials in Children and Adolescents
- ClinicalTrials.gov ID
- NCT03334461
- Acronym / sponsor ID
- IMUNODENT / IP-2014-09-7500
- Conditions
- Caries; Enamel, Gingivitis
- Keywords
- Oral antiseptics, remineralisation agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of RijekaUniversity, hospital or other
- Collaborators
- Croatian Science Foundation
- Study start
- 1 Dec 2015 (actual)
- Primary completion
- 30 Mar 2022 (actual)
- Study completion
- 17 May 2022 (actual)
- First posted
- 7 Nov 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.
During orthodontic treatment intraoral corrosion results with release of nickel and titanium ions from orthodontic appliances in surrounding tissues. Those transported in the saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Nickel is one of the strongest contact allergens, present in numerous dental alloys. The aim of this project is to investigate the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistance of gingivitis to therapy, and bacterial resistance to antibiotics) and changes in performance of orthodontic appliances with repercussion on regeneration of bone and periodontal tissues.
Detailed description
Tooth movement with appliances based on nickel and titanium has got great osteogenic potential and can regenerate deficient parts of alveolar bone and gingiva and rehabilitate compromised occlusal relations and a patient's masticatory function. Due to the extended duration of this therapy, different procedures are carried out and materials are applied for prevention and regeneration of damaged enamel and oral mucosa. The oral cavity may be considered a galvanic cell in which dental alloys act as electrodes, while saliva and oral preventive and regenerative agents act as electrolites. The interaction causes corrosion, reduction of elasticity and increase of stiffness of appliances, which may in turn result in excessive forces, a disruption of tissue regeneration and irreparable damage of tooth roots, surrounding alveolar bone, periodontal ligament, gingiva and pulp.
During the extended exposion, released corrosive products in surrounding tissues and those transported in saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Today, allergies are ever more frequent and arise earlier in life. A specific group are children and young adolescents in pubertal growth, a period in which the immune system develops. Nickel is one of the strongest contact allergens, present in numerous dental alloys. Nickel allergy is occurs in up to 28.5% of population and cannot be deemed as low potential risk anymore.
In contrast, titan was considered a biocompatible material of no allergic potential. However, there is an increase in the frequency of presentations of different hypersensitivity reactions to titan, especially in patients with pacemakers. Numerous patients with hip endoprostheses, stents, dental implans and orthodontic appliances are exposed to titan. Titan allergy may be the cause of unexplained cases of failure and rejection of dental implants. Nickel and titan could cause bacterial resistance to antibiotics which may complicate treatment of a series of infections that are more frequent in children and adolescents.
Regulations for safety of medical products regulate safety issues of materials through mandatory laboratory testing and expertise. However, the testing of interactions of these materials with newly formed materials for prevention of damage and regeneration of orodental tissues is not obligatory prior to the start of their commercial use. Such testing should be conducted by independent scientific insitutions and not by producers with direct commercial interest.
The aim of this project is to investigate:
- the corrosion of dental materials and appliances based on nickel and titan (in saliva and due to interaction with probiotics, remineralising agents and antiseptics)
- the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistency of gingivitis to therapy, and bacterial resistance to antibiotics)
- the effect of nickel and titan ions cellular level
- changes in performance of dental appliances with repercussion on regeneration of bone and periodontal tissues.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized controlled trail
| Arm | Type | Receives |
|---|---|---|
| high concentration enamel remineralisation agent | Experimental | Combination Product: Exposure to oral antiseptics or enamel remineralisation agentfirst month brushing teeth three times per day: twice per day with high-fluorides gel (Mirafluor K gel cola 6150 ppm F pH 5.1) and once per day without toothpaste and fluoride gel next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) |
| oral antiseptic | Experimental | Combination Product: Exposure to oral antiseptics or enamel remineralisation agentfirst month brushing teeth without toothpaste three times per day and using oral antiseptic chlorhexidine mouthwash (Curasept ADS 212 a 200ml 0,12%) twice per day next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) |
| Control | No intervention | –regular oral hygiene without exposure to oral antiseptic or high concentration enamel remineralisation agent three months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- patients with fixed orthodontic appliances
- must be able to do a mouthwash
Key exclusion criteria (1 listed)
- patients allergic to fluoride agents and chlorhexidine gluconate
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 |
|---|---|---|
| Exposure to oral antiseptics or enamel remineralisation agent | Combination product | high concentration enamel remineralisation agent, oral antiseptic |
Primary outcome
Reaction of oral bacterial flora to oral antiseptics and dental remineralisation agents
Time frame: 30 days
Detection of change of count of Streptococcus mutans, sorbinus and salivarius and total bacterial count assesed by qPCR in the dental plaque before and after intervention in patients with fixed orthodontic appliances.
11 secondary outcomes
Dental arch shape
Time frame: 90 days
Oral hygiene
Time frame: 210 days
pH of dental biofilm
Time frame: 210 days
Gingivitis
Time frame: 210 days
Corrosion of dental alloy
Time frame: 90 days
Surface roughness of dental alloy
Time frame: 90 days
Friction of dental alloy
Time frame: 90 days
Forces produced by dental alloy
Time frame: 90 days
Hardness of dental alloy
Time frame: 90 days
Stifness of dental alloy
Time frame: 90 days
Elasticity of dental alloy
Time frame: 90 days
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 26 May 2022.
- Results publication: PubMed 33566077Belasic TZ, Pejova B, Curkovic HO, Kamenar E, Cetenovic B, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Angle Orthod. 2021 Jul 1;91(4):528-537. doi: 10.2319/052620-480.1.
- Results publicationZibar Belasic T, Zigante M, Perkovic V, Uhac M, Spalj S. Comparison of dental and periodontal condition of patients unexposed and exposed to metal orthodontic appliance. Book of Abstracts of the 7th international Congress of School of Dental Medicine University of Zagreb, Rovinj, Croatia, 21.-22.05.2021. Acta Stomatol Croat. 2021;55:213-6.
- Results publicationZibar Belasic T, Zigante M, Uhac M, Karlovic S, Jelovica Badovinac I, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on biomechanics of remodeling of dental arches. 8th Virtual World Congress of Dental Students - Abstract book. Zagreb, Croatia, 2020. p. 2.
- Results publicationCindric L, Mohar Vitezić B, Zigante M, Spalj S, Markova Car E. Changes of bacterial profile of dental biofilm during orthodontic treatment and influence of fluorides and chlorhexidine. South Eur J Orthod Dentofac Res. Conference proceedings - 1st Congress of the Faculty of Dental medicine, University of Rijeka, Croatia, October 1st-3rd 2020. Rijeka, Hrvatska, 2020. p. 55.
- Results publicationZibar Belasic T, Pejova B, Otmacic Curkovic H, Kamenar E, Cetenovic B, Spalj S. Intraoral application of antiseptics and fluorides during orthodontic treatment does not affect significantly corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Prvi kongres Fakulteta dentalne medicine Sveučilišta u Rijeci, Rijeka, 1-2.10.2020. Knjiga sažetaka. South Eur J Orthod Dentofac Res 2020;7:56.
- Results publicationZibar Belasic T, Mohar Vitezic B, Zigante M, Spalj S, Markova Car E. Supragingival biofilm composition changes during orthodontic treatment and chlorhexidine use. Book of Abstracts 97th Annual Congress of the European Orthodontic Society, Limassol, Cipar, 30.05.-03.06.2022.
- all data concerning research project are available at link (Immune and regenerative implications of corrosion of dental materials in children and adolescents)Link provided by the sponsor.
- all data concerning new project are available at link (Environmental factors and microbiological interactions in the structure of dental biofilm)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Stjepan Spalj, PhD principal investigator
University of medicine Rijeka
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Exposure to oral antiseptics or enamel remineralisation agent in people with Caries; Enamel and Gingivitis, run by University of Rijeka 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 2 inclusion and 1 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 26 May 2022. 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. 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?
Reaction of oral bacterial flora to oral antiseptics and dental remineralisation agents (time frame: 30 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 NCT03334461, which also lists 6 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 26 May 2022.