Demineralization, ToothPhase 2NCT06797882
Preventive Effects of Silver Diamine Fluoride on Early Enamel Caries
A Phase 2 study testing Silver diamine fluoride- potassium iodide, Fluoride varnish and 0.9 % saline in people with Demineralization, Tooth and White Spot Lesion of Tooth, run by National University of Malaysia at 1 site in Malaysia.
Trial summary
Fixed orthodontic patients are at risk of developing dental caries. Topical application of fluoride varnish (FV) around the orthodontic brackets and using fluoridated mouth rinses have been suggested to prevent the formation of white spot lesions (WSLs) on enamel. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Demineralization, Tooth, White Spot Lesion of Tooth, Fixed Appliances
- What is being tested?
- Silver diamine fluoride- potassium iodide, Fluoride varnish and 0.9 % saline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 1 siteMalaysia
- Study dates
- 31 Jan 2025to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects about to undergo fixed orthodontic treatment at the Faculty of Dentistry, UKM.
- Subjects must be aged 18 years and above.
- Consented for treatment. Patients will be informed of the risk and benefit of the study for each treatment group through the patient information sheet given to them before obtaining their consent.
- Orthodontic brackets placed at least on the upper incisors.
- Patients undergoing orthodontic treatment with conventional orthodontic brackets placed on the labial surface.
- Any degree of malocclusion
Show all 9Show fewer
- Fit and healthy patient
- Non-smoker
- Subjects can understand and possessed basic command in English
Who cannot join
- History of fixed orthodontic treatment
- Presence of any dental anomalies or developmental defects of enamel (DDE) on labial surfaces of teeth, such as preexisting fluorosis or enamel hypoplasia.
- Presence of any or direct/indirect restorations on the labial surface of teeth
- History of long-term antibiotic usage
- Presence of untreated cavitated lesions, especially on upper and lower incisors and canines
- Plaque levels >30%.
- Patient allergic to any of the content of the intervention material (sodium fluoride, silver diamine fluoride, potassium iodide).
- Patients with lingual brackets.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Malaysia1 site
Faculty of Dentistry, UKM
Kuala Lumpur, Kuala Lumpur, 50300
Ahmad Shuhud Irfani Zakaria, MClinDent, +6012-6137206, shuhud_zakaria@ukm.edu.my
Ahmad Shuhud Irfani Zakaria, MClinDent
About this study
Official title: The Effectiveness of Silver Diamine Fluoride (SDF) in the Prevention of Early Enamel Caries Among Patients With Fixed Orthodontic Appliances: A Randomised Controlled Trial
Fixed orthodontic patients are at risk of developing dental caries. Topical application of fluoride varnish (FV) around the orthodontic brackets and using fluoridated mouth rinses have been suggested to prevent the formation of white spot lesions (WSLs) on enamel. Recent studies have shown that silver diamine fluoride (SDF) demonstrated better outcomes in dental caries prevention as compared to FV. However, the caries preventive effects of SDF application around the orthodontic brackets have not been established yet.
This study will be conducted to evaluate the effectiveness of SDF in preventing WSLs formation in patients undergoing fixed orthodontic treatment. This study will use a randomised-controlled double-blinded design with three parallel arms. Ninety-nine eligible participants will be recruited. Using their registration number, a random list of patients will be generated using computer software. Each patient will be assigned randomly to three groups: SDF, FV, or placebo. Digital photographs of upper anterior teeth (frontal view) will be taken as a baseline and repeated at every review appointment. The materials will be applied around the orthodontic bracket of upper incisors and canines every 6 months. The formation of WSLs around the bracket will be evaluated at 1, 3, 6, and 12 months using three parameters: the ICDAS scoring system, the laser fluorescence caries detector, and digital photographic analysis using the Gorelick score. The patients' perception of the colour changes of the enamel will be evaluated through patient-reported outcomes. The difference in ICDAS and Gorelick scores and the patients' perceptions will be reported through descriptive statistics. The Kruskal-Wallis or one-way ANOVA statistical test will be used to compare the changes in fluorescence intensity between treatment groups.
The investigators believe that the results of this study will provide insight into the caries preventive protocol among fixed orthodontics patients and subsequently reduce the incidence of WSLs during orthodontic treatment.
Read the detailed description
Fixed orthodontic appliances are commonly used to correct malocclusions and align teeth in orthodontic treatment. Fixed orthodontic appliances consist of several components, each serving a specific function in the orthodontic treatment process. These components typically include brackets, arch wires, ligatures (or ties), and occasionally auxiliary components such as springs or elastics. It involves the placement of orthodontic brackets, secured to the teeth surface with a composite resin material. Slots on the brackets are used to hold the orthodontic wires, which act as a means of transmitting forces to the teeth for their movement during orthodontic treatment.
The direct bonding of orthodontic devices to teeth has had a profound impact on orthodontic practices. In the early days of orthodontic treatment, brackets were attached to gold or stainless-steel bands. This process was time-consuming and uncomfortable for patients, often causing gingival trauma and decalcification. In the mid-1960s, researchers pioneered the bonding of brackets directly to enamel. Since then, there have been numerous advancements in adhesives, base designs, bracket materials, curing methods, primers, fluoride-releasing agents, and sealants. Nevertheless, the incidence and severity of white spot lesions caused by enamel decalcification are increasing among those receiving orthodontic treatment. Surprisingly, these lesions can appear as early as one month after the placement of orthodontic brackets. Prolonged treatment, lasting over a year, increases this risk due to the presence of fixed appliances, creating areas for plaque accumulation. This plaque may rapidly modify the composition of bacteria, particularly acid-producing bacteria, leading to enamel erosion and the formation of white spot lesions (WSLs).
White spot lesions are rapidly forming, prompting clinicians to explore solutions for orthodontic-associated demineralization. Factors such as food debris, diet, fluoride availability, mineral crystal composition, and salivary content can influence demineralization periods. Studies have shown that preventive strategies, such as application of topical fluorides, reduce the incidence of WSLs formation. A systematic review has demonstrated the effectiveness of topical sodium fluoride varnishes (FV) in preventing enamel decalcification during orthodontic treatment with fixed appliances. However, the reported preventive fraction is wide, ranging from 12 to 55%. This shows that the preventive effects of FV are not consistent and vary between individuals. The range of results seen may also be attributed to the bioavailability of fluoride in saliva, which is regulated by variables including salivary secretion rate, dietary fluoride consumption, and the usage of fluoridated products. While traditional fluorides like sodium fluoride support remineralization following topical application, they exhibit shorter persistence in saliva compared to SDF's 38% retention. This is due to the stable silver halide compound that forms in saliva, which helps sustain SDF over an extended period of time, and the high fluoride content of SDF, which renders it a great potential for remineralization. Further, the remineralisation and antibacterial effects of fluoride are slow and highly dependent on factors such as patients brushing efficacy and the stability of the fluoride ion in the saliva. This might explain why the WSLs are still occur and present around the orthodontic brackets even though the preventive measures have been implemented.
Recently, the use of silver diamine fluoride (SDF) has gained much attention in caries management strategy, especially on cavitated lesions. SDF was introduced into the dental field by Nishiino, Yamaga and their colleagues in the 1960s available at 38% concentration. SDF is a colourless and odorless solution which consists of silver, fluoride, and ammonia ion. The presence of the silver component in the SDF formulation helps in stimulating dentine sclerosis and provides antibacterial activity by causing immediate bacterial death through inhibition of bacterial DNA replication and blocking the formation of proteolytic enzymes. Fluoride on the other hand act as a remineralising agent and presents at a high concentration of 44,800 ppm.
The combined effects of remineralising and antibacterial properties make SDF an effective cariostatic agent. A systematic review showed that SDF effectively arrests decay in primary teeth in children, with a proportion of 66%-81% with annual or biannual application, while it was reported that the preventive fraction of SDF is as high as 61% and 72%, respectively. In comparison to fluoride varnish, SDF has a better caries arrest ability on both primary and permanent teeth, where the effectiveness is almost doubled than the effects of sodium fluoride varnish at 30 months.
The only drawback of SDF application is the formation of black staining on the cavitated lesion due to the formation of silver phosphate precipitate when hydroxyapatite crystals react with the SDF solution. However, the addition of potassium iodide managed to reduce the staining effects, leading to a yellow-brown rather than a black discoloration. In addition, SDF will not stain sound enamel suggesting its promising role in the prevention of dental caries.
However, based on our knowledge, the effects of SDF in preventing WSLs formation in patients with fixed orthodontics has not been established yet. Therefore, the investigators would like to take this opportunity and conduct a clinical trial with the aim to investigate the effectiveness of Silver Diamine Fluoride (SDF) in caries prevention among patients with fixed orthodontic appliances.
- Conditions
- Demineralization, Tooth, White Spot Lesion of Tooth, Fixed Appliances, Early Caries Lesions
- Being tested
- Silver diamine fluoride- potassium iodide, Fluoride varnish, 0.9 % saline
- Keywords
- Early Caries Lesions, Silver Diamine Fluoride (SDF), Fixed Orthodontic Appliances, Caries Prevention, Fluoride Varnish, White Spot Lesions
- Medical subject headings
- Tooth Demineralization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silver diamine fluoride- potassium iodideDrug
Also called Silver Diamine Fluoride
SDF , Riva Star, SDI Limited., Australia
Fluoride varnishDrug
Duraphat varnish®, Colgate-Palmolive (UK) Ltd.
0.9 % salineOther
Standard oral hygiene instructions every 3 months and application of Normal Saline for every 6 months
| Study group | Role | What they receive |
|---|---|---|
| Standard of care + Silver Diamine Fluoride (SDF) | Experimental | Intervention 1 will receive standard OHI (every three months) and application of Silver Diamine Fluoride (SDF (Riva Star, SDI Limited., Australia) every six months. Receives: Drug: Silver diamine fluoride- potassium iodide |
| Standard of care + Fluoride varnish | Active comparator | Intervention 2 will receive standard OHI (every three months) and application of topical fluoride varnish containing 5% NaF (Duraphat varnish®, Colgate-Palmolive (UK) Ltd) every six months. Receives: Drug: Fluoride varnish |
| Standard of care + Normal Saline | Placebo comparator | Control will receive standard oral hygiene instructions (OHI every three months) and application of normal saline every six months. Receives: Other: 0.9 % saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Formation of Early Enamel Caries Analyzed Through Digital Photography
Changes in enamel surface following decalcification, measured using the Gorelick's Index (1982) in all three intervention groups.
Gorelick's Index Scale:
0 - No lesion (best outcome)
- - Moderate lesion
- - Severe lesion
- - Cavitation (worst outcome) Lower scores represent better outcomes, while higher scores indicate poorer outcomes.
Measured: 12 months
Formation of Early Enamel Caries Assessed Clinically by a Blinded Assessor
Changes in enamel surface following decalcification, measured clinically using the International Caries Detection and Assessment System II (ICDAS II) Index (2005) in all three intervention groups.
ICDAS II Scale:
0 - Sound tooth surface: No evidence of caries after 5 seconds of air drying (best outcome)
- - First visual change in enamel: Opacity or discoloration (white or brown) visible after prolonged air drying
- - Distinct visual change in enamel visible when wet; lesion must be visible when dry
- - Localized enamel breakdown (without clinical visual signs of dentinal involvement), seen when wet and after prolonged drying
- - Underlying dark shadow from dentine
- - Distinct cavity with visible dentine
- - Extensive (more than half the surface) distinct cavity with visible dentine (worst outcome) Lower scores represent better outcomes, while higher scores indicate poorer outcomes.
Measured: 12 months
Change in Laser Fluorescence Values
Changes in mean DIAGNOdent scores among the three study groups.
DIAGNOdent Scale:
0-13 - Sound tooth surface (best outcome) 14-20 - Enamel caries >20 - Dentinal caries (worst outcome) Lower readings represent better outcomes, while higher readings indicate poorer outcomes.
Measured: 12 months
Participants Perspectives on Tooth Colour Changes After Silver Diamine Fluoride (SDF) Application: Participants-Reported Outcome
Participants perceptions of visible colour changes following SDF application will be evaluated using a structured questionnaire at baseline and follow-up appointments (1, 3, 6, and 12 months). Participants will report whether they notice any colour changes and indicate their satisfaction with the appearance of their teeth.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start31 Jan 2025 (estimated)
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Demineralization, ToothStudies 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
- This study follows a randomized controlled trial design with three parallel groups. Each participant, rather than specific areas within the mouth, will be the unit of randomization. This method, in contrast to a split-mouth design, helps prevent issues related to cross-contamination.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University of Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmad Shuhud Irfani bin Zakaria, National University of Malaysia
- Investigators
- Ahmad Shuhud Irfani Zakaria, MClinDent, Principal investigator, National University of Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06797882
- Sponsor's protocol ID
- JEP-2024-878
- Status last verified
- Jan 2025
- First submitted
- 27 Jan 2025
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data will be submitted to the university repository and final data will be deposited to the university. Patient personal information will be protected and subjected to Data Security Act.
Publications
Mungur A, Chen H, Shahid S, Baysan A. A systematic review on the effect of silver diamine fluoride for management of dental caries in permanent teeth. Clin Exp Dent Res. 2023 Apr;9(2):375-387. doi: 10.1002/cre2.716. Epub 2023 Feb 23.
PubMed 36823765Lussi A, Megert B, Longbottom C, Reich E, Francescut P. Clinical performance of a laser fluorescence device for detection of occlusal caries lesions. Eur J Oral Sci. 2001 Feb;109(1):14-9. doi: 10.1034/j.1600-0722.2001.109001014.x.
PubMed 11330928Lazar L, Vlasa A, Beresescu L, Bud A, Lazar AP, Matei L, Bud E. White Spot Lesions (WSLs)-Post-Orthodontic Occurrence, Management and Treatment Alternatives: A Narrative Review. J Clin Med. 2023 Feb 28;12(5):1908. doi: 10.3390/jcm12051908.
PubMed 36902696Jabin Z, Nasim I, Priya V V, Agarwal N. Comparative Evaluation of Salivary Fluoride Concentration after Topical Application of Silver Diamine Fluoride and Sodium Fluoride: A Randomized Controlled Trial. Int J Clin Pediatr Dent. 2022 May-Jun;15(3):371-375. doi: 10.5005/jp-journals-10005-2398.
PubMed 35991787Hicks J, Garcia-Godoy F, Flaitz C. Biological factors in dental caries: role of remineralization and fluoride in the dynamic process of demineralization and remineralization (part 3). J Clin Pediatr Dent. 2004 Spring;28(3):203-14. doi: 10.17796/jcpd.28.3.w0610427l746j34n.
PubMed 15163148Gange P. The evolution of bonding in orthodontics. Am J Orthod Dentofacial Orthop. 2015 Apr;147(4 Suppl):S56-63. doi: 10.1016/j.ajodo.2015.01.011.
PubMed 25836345Seifo N, Robertson M, MacLean J, Blain K, Grosse S, Milne R, Seeballuck C, Innes N. The use of silver diamine fluoride (SDF) in dental practice. Br Dent J. 2020 Jan;228(2):75-81. doi: 10.1038/s41415-020-1203-9.
PubMed 31980777Tufekci E, Dixon JS, Gunsolley JC, Lindauer SJ. Prevalence of white spot lesions during orthodontic treatment with fixed appliances. Angle Orthod. 2011 Mar;81(2):206-10. doi: 10.2319/051710-262.1.
PubMed 21208070Sonesson M, Twetman S. Prevention of white spot lesions with fluoride varnish during orthodontic treatment with fixed appliances: a systematic review. Eur J Orthod. 2023 Sep 18;45(5):485-490. doi: 10.1093/ejo/cjad013.
PubMed 37032523Sardana D, Ekambaram M, Yang Y, McGrath CP, Yiu CKY. Caries-preventive effectiveness of two different fluoride varnishes: A randomised clinical trial in patients with multi-bracketed fixed orthodontic appliances. Int J Paediatr Dent. 2023 Jan;33(1):50-62. doi: 10.1111/ipd.13013. Epub 2022 Jul 10.
PubMed 35737872Sardana D, Li KY, Ekambaram M, Yang Y, McGrath CP, Yiu CK. Validation of clinical photography and a laser fluorescence device for assessment of enamel demineralization during multi-bracketed fixed orthodontic treatment. Photodiagnosis Photodyn Ther. 2022 Jun;38:102828. doi: 10.1016/j.pdpdt.2022.102828. Epub 2022 Mar 23.
PubMed 35339722Kidd E, Fejerskov O. Changing concepts in cariology: forty years on. Dent Update. 2013 May;40(4):277-8, 280-2, 285-6. doi: 10.12968/denu.2013.40.4.277.
PubMed 23829008Jiang H, Hua F, Yao L, Tai B, Du M. Effect of 1.23% acidulated phosphate fluoride foam on white spot lesions in orthodontic patients: a randomized trial. Pediatr Dent. 2013 May-Jun;35(3):275-8.
PubMed 23756315Ismail AI, Sohn W, Tellez M, Amaya A, Sen A, Hasson H, Pitts NB. The International Caries Detection and Assessment System (ICDAS): an integrated system for measuring dental caries. Community Dent Oral Epidemiol. 2007 Jun;35(3):170-8. doi: 10.1111/j.1600-0528.2007.00347.x.
PubMed 17518963Horst JA, Heima M. Prevention of Dental Caries by Silver Diamine Fluoride. Compend Contin Educ Dent. 2019 Mar;40(3):158-163; quiz 164.
PubMed 30829497
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Silver Diamine Fluoride (SDF) in the Prevention of Early Enamel Caries Among Patients With Fixed Orthodontic Appliances: A Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT06797882
- Acronym / sponsor ID
- JEP-2024-878
- Conditions
- Demineralization, Tooth, White Spot Lesion of Tooth, Fixed Appliances, Early Caries Lesions
- Keywords
- Early Caries Lesions, Silver Diamine Fluoride (SDF), Fixed Orthodontic Appliances, Caries Prevention, Fluoride Varnish, White Spot Lesions
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- National University of MalaysiaUniversity, hospital or other
- Study start
- 31 Jan 2025 (estimated)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 29 Jan 2025 (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.
Fixed orthodontic patients are at risk of developing dental caries. Topical application of fluoride varnish (FV) around the orthodontic brackets and using fluoridated mouth rinses have been suggested to prevent the formation of white spot lesions (WSLs) on enamel. Recent studies have shown that silver diamine fluoride (SDF) demonstrated better outcomes in dental caries prevention as compared to FV. However, the caries preventive effects of SDF application around the orthodontic brackets have not been established yet.
This study will be conducted to evaluate the effectiveness of SDF in preventing WSLs formation in patients undergoing fixed orthodontic treatment. This study will use a randomised-controlled double-blinded design with three parallel arms. Ninety-nine eligible participants will be recruited. Using their registration number, a random list of patients will be generated using computer software. Each patient will be assigned randomly to three groups: SDF, FV, or placebo. Digital photographs of upper anterior teeth (frontal view) will be taken as a baseline and repeated at every review appointment. The materials will be applied around the orthodontic bracket of upper incisors and canines every 6 months. The formation of WSLs around the bracket will be evaluated at 1, 3, 6, and 12 months using three parameters: the ICDAS scoring system, the laser fluorescence caries detector, and digital photographic analysis using the Gorelick score. The patients' perception of the colour changes of the enamel will be evaluated through patient-reported outcomes. The difference in ICDAS and Gorelick scores and the patients' perceptions will be reported through descriptive statistics. The Kruskal-Wallis or one-way ANOVA statistical test will be used to compare the changes in fluorescence intensity between treatment groups.
The investigators believe that the results of this study will provide insight into the caries preventive protocol among fixed orthodontics patients and subsequently reduce the incidence of WSLs during orthodontic treatment.
Detailed description
Fixed orthodontic appliances are commonly used to correct malocclusions and align teeth in orthodontic treatment. Fixed orthodontic appliances consist of several components, each serving a specific function in the orthodontic treatment process. These components typically include brackets, arch wires, ligatures (or ties), and occasionally auxiliary components such as springs or elastics. It involves the placement of orthodontic brackets, secured to the teeth surface with a composite resin material. Slots on the brackets are used to hold the orthodontic wires, which act as a means of transmitting forces to the teeth for their movement during orthodontic treatment.
The direct bonding of orthodontic devices to teeth has had a profound impact on orthodontic practices. In the early days of orthodontic treatment, brackets were attached to gold or stainless-steel bands. This process was time-consuming and uncomfortable for patients, often causing gingival trauma and decalcification. In the mid-1960s, researchers pioneered the bonding of brackets directly to enamel. Since then, there have been numerous advancements in adhesives, base designs, bracket materials, curing methods, primers, fluoride-releasing agents, and sealants. Nevertheless, the incidence and severity of white spot lesions caused by enamel decalcification are increasing among those receiving orthodontic treatment. Surprisingly, these lesions can appear as early as one month after the placement of orthodontic brackets. Prolonged treatment, lasting over a year, increases this risk due to the presence of fixed appliances, creating areas for plaque accumulation. This plaque may rapidly modify the composition of bacteria, particularly acid-producing bacteria, leading to enamel erosion and the formation of white spot lesions (WSLs).
White spot lesions are rapidly forming, prompting clinicians to explore solutions for orthodontic-associated demineralization. Factors such as food debris, diet, fluoride availability, mineral crystal composition, and salivary content can influence demineralization periods. Studies have shown that preventive strategies, such as application of topical fluorides, reduce the incidence of WSLs formation. A systematic review has demonstrated the effectiveness of topical sodium fluoride varnishes (FV) in preventing enamel decalcification during orthodontic treatment with fixed appliances. However, the reported preventive fraction is wide, ranging from 12 to 55%. This shows that the preventive effects of FV are not consistent and vary between individuals. The range of results seen may also be attributed to the bioavailability of fluoride in saliva, which is regulated by variables including salivary secretion rate, dietary fluoride consumption, and the usage of fluoridated products. While traditional fluorides like sodium fluoride support remineralization following topical application, they exhibit shorter persistence in saliva compared to SDF's 38% retention. This is due to the stable silver halide compound that forms in saliva, which helps sustain SDF over an extended period of time, and the high fluoride content of SDF, which renders it a great potential for remineralization. Further, the remineralisation and antibacterial effects of fluoride are slow and highly dependent on factors such as patients brushing efficacy and the stability of the fluoride ion in the saliva. This might explain why the WSLs are still occur and present around the orthodontic brackets even though the preventive measures have been implemented.
Recently, the use of silver diamine fluoride (SDF) has gained much attention in caries management strategy, especially on cavitated lesions. SDF was introduced into the dental field by Nishiino, Yamaga and their colleagues in the 1960s available at 38% concentration. SDF is a colourless and odorless solution which consists of silver, fluoride, and ammonia ion. The presence of the silver component in the SDF formulation helps in stimulating dentine sclerosis and provides antibacterial activity by causing immediate bacterial death through inhibition of bacterial DNA replication and blocking the formation of proteolytic enzymes. Fluoride on the other hand act as a remineralising agent and presents at a high concentration of 44,800 ppm.
The combined effects of remineralising and antibacterial properties make SDF an effective cariostatic agent. A systematic review showed that SDF effectively arrests decay in primary teeth in children, with a proportion of 66%-81% with annual or biannual application, while it was reported that the preventive fraction of SDF is as high as 61% and 72%, respectively. In comparison to fluoride varnish, SDF has a better caries arrest ability on both primary and permanent teeth, where the effectiveness is almost doubled than the effects of sodium fluoride varnish at 30 months.
The only drawback of SDF application is the formation of black staining on the cavitated lesion due to the formation of silver phosphate precipitate when hydroxyapatite crystals react with the SDF solution. However, the addition of potassium iodide managed to reduce the staining effects, leading to a yellow-brown rather than a black discoloration. In addition, SDF will not stain sound enamel suggesting its promising role in the prevention of dental caries.
However, based on our knowledge, the effects of SDF in preventing WSLs formation in patients with fixed orthodontics has not been established yet. Therefore, the investigators would like to take this opportunity and conduct a clinical trial with the aim to investigate the effectiveness of Silver Diamine Fluoride (SDF) in caries prevention among patients with fixed orthodontic appliances.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- This study follows a randomized controlled trial design with three parallel groups. Each participant, rather than specific areas within the mouth, will be the unit of randomization. This method, in contrast to a split-mouth design, helps prevent issues related to cross-contamination.
| Arm | Type | Receives |
|---|---|---|
| Standard of care + Silver Diamine Fluoride (SDF) | Experimental | Drug: Silver diamine fluoride- potassium iodideIntervention 1 will receive standard OHI (every three months) and application of Silver Diamine Fluoride (SDF (Riva Star, SDI Limited., Australia) every six months. |
| Standard of care + Fluoride varnish | Active comparator | Drug: Fluoride varnishIntervention 2 will receive standard OHI (every three months) and application of topical fluoride varnish containing 5% NaF (Duraphat varnish®, Colgate-Palmolive (UK) Ltd) every six months. |
| Standard of care + Normal Saline | Placebo comparator | Other: 0.9 % salineControl will receive standard oral hygiene instructions (OHI every three months) and application of normal saline every six months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects about to undergo fixed orthodontic treatment at the Faculty of Dentistry, UKM.
- Subjects must be aged 18 years and above.
- Consented for treatment. Patients will be informed of the risk and benefit of the study for each treatment group through the patient information sheet given to them before obtaining their consent.
- Orthodontic brackets placed at least on the upper incisors.
- Patients undergoing orthodontic treatment with conventional orthodontic brackets placed on the labial surface.
Key exclusion criteria (8 listed)
- History of fixed orthodontic treatment
- Presence of any dental anomalies or developmental defects of enamel (DDE) on labial surfaces of teeth, such as preexisting fluorosis or enamel hypoplasia.
- Presence of any or direct/indirect restorations on the labial surface of teeth
- History of long-term antibiotic usage
- Presence of untreated cavitated lesions, especially on upper and lower incisors and canines
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 |
|---|---|---|
| Silver diamine fluoride- potassium iodideAlso: Silver Diamine FluorideSDF , Riva Star, SDI Limited., Australia | Drug | Standard of care + Silver Diamine Fluoride (SDF) |
| Fluoride varnishDuraphat varnish®, Colgate-Palmolive (UK) Ltd. | Drug | Standard of care + Fluoride varnish |
| 0.9 % salineStandard oral hygiene instructions every 3 months and application of Normal Saline for every 6 months | Other | Standard of care + Normal Saline |
Primary outcome
Formation of Early Enamel Caries Analyzed Through Digital Photography
Time frame: 12 months
Changes in enamel surface following decalcification, measured using the Gorelick's Index (1982) in all three intervention groups. Gorelick's Index Scale: 0 - No lesion (best outcome) 1. - Moderate lesion 2. - Severe lesion 3. - Cavitation (worst outcome) Lower scores represent better outcomes, while higher scores indicate poorer outcomes.
Formation of Early Enamel Caries Assessed Clinically by a Blinded Assessor
Time frame: 12 months
Changes in enamel surface following decalcification, measured clinically using the International Caries Detection and Assessment System II (ICDAS II) Index (2005) in all three intervention groups. ICDAS II Scale: 0 - Sound tooth surface: No evidence of caries after 5 seconds of air drying (best outcome) 1. - First visual change in enamel: Opacity or discoloration (white or brown) visible after prolonged air drying 2. - Distinct visual change in enamel visible when wet; lesion must be visible when dry 3. - Localized enamel breakdown (without clinical visual signs of dentinal involvement), seen when wet and after prolonged drying 4. - Underlying dark shadow from dentine 5. - Distinct cavity with visible dentine 6. - Extensive (more than half the surface) distinct cavity with visible dentine (worst outcome) Lower scores represent better outcomes, while higher scores indicate poorer outcomes.
Change in Laser Fluorescence Values
Time frame: 12 months
Changes in mean DIAGNOdent scores among the three study groups. DIAGNOdent Scale: 0-13 - Sound tooth surface (best outcome) 14-20 - Enamel caries >20 - Dentinal caries (worst outcome) Lower readings represent better outcomes, while higher readings indicate poorer outcomes.
Participants Perspectives on Tooth Colour Changes After Silver Diamine Fluoride (SDF) Application: Participants-Reported Outcome
Time frame: 12 months
Participants perceptions of visible colour changes following SDF application will be evaluated using a structured questionnaire at baseline and follow-up appointments (1, 3, 6, and 12 months). Participants will report whether they notice any colour changes and indicate their satisfaction with the appearance of their teeth.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Background: PubMed 36823765Mungur A, Chen H, Shahid S, Baysan A. A systematic review on the effect of silver diamine fluoride for management of dental caries in permanent teeth. Clin Exp Dent Res. 2023 Apr;9(2):375-387. doi: 10.1002/cre2.716. Epub 2023 Feb 23.
- Background: PubMed 11330928Lussi A, Megert B, Longbottom C, Reich E, Francescut P. Clinical performance of a laser fluorescence device for detection of occlusal caries lesions. Eur J Oral Sci. 2001 Feb;109(1):14-9. doi: 10.1034/j.1600-0722.2001.109001014.x.
- Background: PubMed 36902696Lazar L, Vlasa A, Beresescu L, Bud A, Lazar AP, Matei L, Bud E. White Spot Lesions (WSLs)-Post-Orthodontic Occurrence, Management and Treatment Alternatives: A Narrative Review. J Clin Med. 2023 Feb 28;12(5):1908. doi: 10.3390/jcm12051908.
- Background: PubMed 35991787Jabin Z, Nasim I, Priya V V, Agarwal N. Comparative Evaluation of Salivary Fluoride Concentration after Topical Application of Silver Diamine Fluoride and Sodium Fluoride: A Randomized Controlled Trial. Int J Clin Pediatr Dent. 2022 May-Jun;15(3):371-375. doi: 10.5005/jp-journals-10005-2398.
- Background: PubMed 15163148Hicks J, Garcia-Godoy F, Flaitz C. Biological factors in dental caries: role of remineralization and fluoride in the dynamic process of demineralization and remineralization (part 3). J Clin Pediatr Dent. 2004 Spring;28(3):203-14. doi: 10.17796/jcpd.28.3.w0610427l746j34n.
- Background: PubMed 25836345Gange P. The evolution of bonding in orthodontics. Am J Orthod Dentofacial Orthop. 2015 Apr;147(4 Suppl):S56-63. doi: 10.1016/j.ajodo.2015.01.011.
- Background: PubMed 31980777Seifo N, Robertson M, MacLean J, Blain K, Grosse S, Milne R, Seeballuck C, Innes N. The use of silver diamine fluoride (SDF) in dental practice. Br Dent J. 2020 Jan;228(2):75-81. doi: 10.1038/s41415-020-1203-9.
- Background: PubMed 21208070Tufekci E, Dixon JS, Gunsolley JC, Lindauer SJ. Prevalence of white spot lesions during orthodontic treatment with fixed appliances. Angle Orthod. 2011 Mar;81(2):206-10. doi: 10.2319/051710-262.1.
- Background: PubMed 37032523Sonesson M, Twetman S. Prevention of white spot lesions with fluoride varnish during orthodontic treatment with fixed appliances: a systematic review. Eur J Orthod. 2023 Sep 18;45(5):485-490. doi: 10.1093/ejo/cjad013.
- Background: PubMed 35737872Sardana D, Ekambaram M, Yang Y, McGrath CP, Yiu CKY. Caries-preventive effectiveness of two different fluoride varnishes: A randomised clinical trial in patients with multi-bracketed fixed orthodontic appliances. Int J Paediatr Dent. 2023 Jan;33(1):50-62. doi: 10.1111/ipd.13013. Epub 2022 Jul 10.
- Background: PubMed 35339722Sardana D, Li KY, Ekambaram M, Yang Y, McGrath CP, Yiu CK. Validation of clinical photography and a laser fluorescence device for assessment of enamel demineralization during multi-bracketed fixed orthodontic treatment. Photodiagnosis Photodyn Ther. 2022 Jun;38:102828. doi: 10.1016/j.pdpdt.2022.102828. Epub 2022 Mar 23.
- Background: PubMed 23829008Kidd E, Fejerskov O. Changing concepts in cariology: forty years on. Dent Update. 2013 May;40(4):277-8, 280-2, 285-6. doi: 10.12968/denu.2013.40.4.277.
- Individual participant dataSharing planned: Undecided. Data will be submitted to the university repository and final data will be deposited to the university. Patient personal information will be protected and subjected to Data Security Act.
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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.
Ahmad Shuhud Irfani Zakaria, MClinDent principal investigator
National University of Malaysia
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 Silver diamine fluoride- potassium iodide, Fluoride varnish and 0.9 % saline in people with Demineralization, Tooth and White Spot Lesion of Tooth, run by National University of Malaysia at 1 site in Malaysia.
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 9 inclusion and 8 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: opening soon, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Muhd Ja'afar Siddique Mohd Hafizan, BDMS (+60136408105, p153628@siswa.ukm.edu.my), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Formation of Early Enamel Caries Analyzed Through Digital Photography (time frame: 12 months). The study lists 4 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 NCT06797882, which also lists 21 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 30 Jan 2025.