White Spot LesionsNCT07229105
Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients
A study testing GC Tooth Mousse, Nano-Hydroxyapatite Gel and Sodium Fluoride varnish in people with White Spot Lesions and Demineralization, run by Bezmialem Vakif University at 1 site in Turkey (Türkiye).
Trial summary
Background/ Objectives: Clear aligner attachments increase the risk of white spot lesions (WSL), with a 35.5% incidence in adolescents. The number of anterior attachments is an independent risk factor (OR=2.192). Read more about this study
- Who is it for?
- Ages 16 to 45 years
- Conditions the study is for
- White Spot Lesions, Demineralization, Dental Caries
- What is being tested?
- GC Tooth Mousse, Nano-Hydroxyapatite Gel and Sodium Fluoride varnish
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 12 Aug 2024to 28 Mar 2025
- Phase
- Interventional
- 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 16 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 16-45 years
- Active clear aligner treatment with minimum 6 months remaining
- Presence of ≥10 attachments on anterior teeth and premolars
- Good general health
- Commitment to prescribed aligner wear (20-22 hours/day)
Who cannot join
- Active carious lesions
- Periodontal disease
- Fluorosis or enamel hypoplasia
- Current fluoride supplement use beyond standard toothpaste
- Pregnancy or lactation
- Systemic conditions affecting salivary flow
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Bezmialem Vakif University, Faculty of Dentistry
Istanbul
About this study
Official title: Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients: A 6-Month DIAGNOdent-Based Observational Study
Background/ Objectives: Clear aligner attachments increase the risk of white spot lesions (WSL), with a 35.5% incidence in adolescents. The number of anterior attachments is an independent risk factor (OR=2.192). Despite 17 million patients treated worldwide, no study has quantitatively assessed demineralization around attachment margins. To compare the effectiveness of CPP-ACP, nano-hydroxyapatite (nHAp), and fluoride varnish versus a control for attachment-associated demineralization using DIAGNOdent monitoring.
Methods: This prospective observational study evaluated 52 patients; 45 were enrolled, and 40 completed after five pre-baseline withdrawals. Participants were allocated to four groups (n=10 each): Group A (control, fluoride toothpaste), Group B (CPP-ACP daily), Group C (nHAp professional + home gel), and Group D (fluoride varnish quarterly). DIAGNOdent measurements were taken around attachments at baseline, 1, 3, and 6 months. Linear mixed-effects models analyzed group differences (p<0.05).
Read the detailed description
DIAGNOdent Measurement Protocol Calibration and Standardization The DIAGNOdent pen (KaVo, Biberach, Germany) was calibrated before each measurement session according to the manufacturer's instructions using a ceramic standard[18]. A single calibrated examiner performed all measurements to ensure consistency. Intra-examiner reliability was assessed using intraclass correlation coefficient (ICC) with two-way mixed model, absolute agreement, calculated from 30 repeated measurements at 10 randomly selected attachment sites (ICC = 0.85, 95% CI: 0.79-0.91).
Measurement Technique A standardized measurement protocol was employed for all DIAGNOdent assessments. Teeth were air-dried for 5 seconds prior to measurement, and the probe tip was positioned perpendicular to the enamel surface to ensure consistent readings. Four measurements were obtained per attachment site at the mesial, distal, gingival, and occlusal margins. Three measurement passes were performed at each site, with the maximum value recorded to represent the most advanced demineralization present. Measurements were conducted at four timepoints: baseline (T0), 1 month (T1), 3 months (T2), and 6 months (T3).
- Being tested
- GC Tooth Mousse, Nano-Hydroxyapatite Gel, Sodium Fluoride varnish
- Keywords
- clear aligners, Orthodontic Attachments, DIAGNOdent, White Spot Lesions, White Spot Lesion
- Medical subject headings
- Dental Caries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GC Tooth MousseDevice
Also called CPP-ACP Paste
Participants applied a pea-sized amount of GC Tooth Mousse into each aligner once daily before bedtime. They wore the aligners with the mousse for 15 minutes and were instructed not to rinse for 30 minutes post-application.
Nano-Hydroxyapatite GelDevice
Also called BioWhiten ProOffice and Nanocare
A combined protocol involving: 1) Professional in-office application of 5% nHAp gel (BioWhiten ProOffice) at baseline, 1 month, and 3 months; and 2) Daily home application of 1% nHAp gel (Biowhiten Nanocare) into aligners every night before sleep.
Sodium Fluoride varnishDrug
Also called ProShield Varnish
Professional application of 5% sodium fluoride varnish (ProShield) to all tooth surfaces, with special attention to attachment margins, at baseline and 3 months. The varnish was left for 1 minute contact time before removal, with instructions not to eat/drink for 2 hours.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Control | No intervention | The participants used standard fluoride toothpaste (1450 ppm) twice daily, with no additional remineralization protocol. |
| Group B: Casein Phosphopeptide-Amorphous Calcium Phosphate | Experimental | In addition to standard fluoride toothpaste, participants applied GC Tooth Mousse (CPP-ACP) to their clear aligners once daily for 15 minutes before bedtime. Receives: Device: GC Tooth Mousse |
| Group C: Nano-Hydroxyapatite | Experimental | Professional in-office application of 5% nHAp gel at baseline, 1, and 3 months, combined with daily home application of 1% nHAp gel into aligners. Receives: Device: Nano-Hydroxyapatite Gel |
| Group D: Professional Fluoride Varnish | Experimental | Professional application of 5% sodium fluoride varnish (ProShield) applied to attachment margins at baseline and 3 months. Receives: Drug: Sodium Fluoride varnish |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Enamel Demineralization (DIAGNOdent values).
Measurements taken using DIAGNOdent pen around attachment margins. Validated cut-off values: 0-12 sound, 13-24 initial, >25 advanced.
Measured: Baseline (T0) to 6 months (T3).
Secondary outcomes (1)
Temporal Changes in Enamel Mineralization
Evaluation of DIAGNOdent values at intermediate time points to assess the progression or regression patterns (e.g., continuous improvement vs. biphasic response) of demineralization.
Measured: 1 month (T1) and 3 months (T2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2025
- Study start12 Aug 2024
- Primary completion28 Mar 2025
- Study completion28 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for White Spot LesionsStudies of the same condition, open and under way.
- More trials run by Bezmialem Vakif UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bezmialem Vakif University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Banu Kılıç, Bezmialem Vakif University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07229105
- Sponsor's protocol ID
- 09/15
- Status last verified
- Nov 2025
- First submitted
- 13 Nov 2025
- Last updated
- 14 Nov 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
Publications
Unal HY, Kilic B, Dalkilic EE. Comparative effectiveness of remineralization agents on attachment-associated enamel demineralization in clear aligner patients: A 6-Month DIAGNOdent-Based controlled clinical trial. BMC Oral Health. 2025 Dec 11;26(1):96. doi: 10.1186/s12903-025-07497-8.
PubMed 41382095
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients: A 6-Month DIAGNOdent-Based Observational Study
- ClinicalTrials.gov ID
- NCT07229105
- Acronym / sponsor ID
- 09/15
- Keywords
- clear aligners, Orthodontic Attachments, DIAGNOdent, White Spot Lesions, White Spot Lesion
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Bezmialem Vakif UniversityUniversity, hospital or other
- Study start
- 12 Aug 2024 (actual)
- Primary completion
- 28 Mar 2025 (actual)
- Study completion
- 28 Mar 2025 (actual)
- First posted
- 14 Nov 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.
Background/ Objectives: Clear aligner attachments increase the risk of white spot lesions (WSL), with a 35.5% incidence in adolescents. The number of anterior attachments is an independent risk factor (OR=2.192). Despite 17 million patients treated worldwide, no study has quantitatively assessed demineralization around attachment margins. To compare the effectiveness of CPP-ACP, nano-hydroxyapatite (nHAp), and fluoride varnish versus a control for attachment-associated demineralization using DIAGNOdent monitoring.
Methods: This prospective observational study evaluated 52 patients; 45 were enrolled, and 40 completed after five pre-baseline withdrawals. Participants were allocated to four groups (n=10 each): Group A (control, fluoride toothpaste), Group B (CPP-ACP daily), Group C (nHAp professional + home gel), and Group D (fluoride varnish quarterly). DIAGNOdent measurements were taken around attachments at baseline, 1, 3, and 6 months. Linear mixed-effects models analyzed group differences (p<0.05).
Detailed description
DIAGNOdent Measurement Protocol Calibration and Standardization The DIAGNOdent pen (KaVo, Biberach, Germany) was calibrated before each measurement session according to the manufacturer's instructions using a ceramic standard[18]. A single calibrated examiner performed all measurements to ensure consistency. Intra-examiner reliability was assessed using intraclass correlation coefficient (ICC) with two-way mixed model, absolute agreement, calculated from 30 repeated measurements at 10 randomly selected attachment sites (ICC = 0.85, 95% CI: 0.79-0.91).
Measurement Technique A standardized measurement protocol was employed for all DIAGNOdent assessments. Teeth were air-dried for 5 seconds prior to measurement, and the probe tip was positioned perpendicular to the enamel surface to ensure consistent readings. Four measurements were obtained per attachment site at the mesial, distal, gingival, and occlusal margins. Three measurement passes were performed at each site, with the maximum value recorded to represent the most advanced demineralization present. Measurements were conducted at four timepoints: baseline (T0), 1 month (T1), 3 months (T2), and 6 months (T3).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A: Control | No intervention | –The participants used standard fluoride toothpaste (1450 ppm) twice daily, with no additional remineralization protocol. |
| Group B: Casein Phosphopeptide-Amorphous Calcium Phosphate | Experimental | Device: GC Tooth MousseIn addition to standard fluoride toothpaste, participants applied GC Tooth Mousse (CPP-ACP) to their clear aligners once daily for 15 minutes before bedtime. |
| Group C: Nano-Hydroxyapatite | Experimental | Device: Nano-Hydroxyapatite GelProfessional in-office application of 5% nHAp gel at baseline, 1, and 3 months, combined with daily home application of 1% nHAp gel into aligners. |
| Group D: Professional Fluoride Varnish | Experimental | Drug: Sodium Fluoride varnishProfessional application of 5% sodium fluoride varnish (ProShield) applied to attachment margins at baseline and 3 months. |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age 16-45 years
- Active clear aligner treatment with minimum 6 months remaining
- Presence of ≥10 attachments on anterior teeth and premolars
- Good general health
- Commitment to prescribed aligner wear (20-22 hours/day)
Key exclusion criteria (6 listed)
- Active carious lesions
- Periodontal disease
- Fluorosis or enamel hypoplasia
- Current fluoride supplement use beyond standard toothpaste
- Pregnancy or lactation
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 |
|---|---|---|
| GC Tooth MousseAlso: CPP-ACP PasteParticipants applied a pea-sized amount of GC Tooth Mousse into each aligner once daily before bedtime. They wore the aligners with the mousse for 15 minutes and were instructed not to rinse for 30 minutes post-application. | Device | Group B: Casein Phosphopeptide-Amorphous Calcium Phosphate |
| Nano-Hydroxyapatite GelAlso: BioWhiten ProOffice and NanocareA combined protocol involving: 1) Professional in-office application of 5% nHAp gel (BioWhiten ProOffice) at baseline, 1 month, and 3 months; and 2) Daily home application of 1% nHAp gel (Biowhiten Nanocare) into aligners every night before sleep. | Device | Group C: Nano-Hydroxyapatite |
| Sodium Fluoride varnishAlso: ProShield VarnishProfessional application of 5% sodium fluoride varnish (ProShield) to all tooth surfaces, with special attention to attachment margins, at baseline and 3 months. The varnish was left for 1 minute contact time before removal, with instructions not to eat/drink for 2 hours. | Drug | Group D: Professional Fluoride Varnish |
Primary outcome
Change in Enamel Demineralization (DIAGNOdent values).
Time frame: Baseline (T0) to 6 months (T3).
Measurements taken using DIAGNOdent pen around attachment margins. Validated cut-off values: 0-12 sound, 13-24 initial, >25 advanced.
1 secondary outcome
Temporal Changes in Enamel Mineralization
Time frame: 1 month (T1) and 3 months (T2)
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 14 Nov 2025.
- Derived from this study: PubMed 41382095Unal HY, Kilic B, Dalkilic EE. Comparative effectiveness of remineralization agents on attachment-associated enamel demineralization in clear aligner patients: A 6-Month DIAGNOdent-Based controlled clinical trial. BMC Oral Health. 2025 Dec 11;26(1):96. doi: 10.1186/s12903-025-07497-8.
- Individual participant dataSharing planned: Yes. The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GC Tooth Mousse, Nano-Hydroxyapatite Gel and Sodium Fluoride varnish in people with White Spot Lesions and Demineralization, run by Bezmialem Vakif University at 1 site in Turkey (Türkiye).
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 5 inclusion and 6 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 14 Nov 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 Turkey (Türkiye). 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.
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?
Change in Enamel Demineralization (DIAGNOdent values). (time frame: Baseline (T0) to 6 months (T3).). 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 NCT07229105, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2025.