Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients

Not Applicable

Completed

• Conditions: White Spot Lesions; Demineralization; Dental Caries; Orthodontic Treatment
• Interventions: Device: GC Tooth Mousse; Device: Nano-Hydroxyapatite Gel; Drug: Sodium Fluoride varnish

• Registration Number: NCT07229105
• Lead Sponsor: Bezmialem Vakif University

Brief 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). 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 Timeline

• Study Start: 2024-08-12
• Primary Completion: 2025-03-28
• Study Completion: 2025-03-28
• Status Verified: 2025-11
• Study First Submitted: 2025-11-13
• Study First Submitted QC: 2025-11-13
• Last Update Submitted: 2025-11-13
• Study First Posted: 2025-11-14
• Last Update Posted: 2025-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 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)

Exclusion Criteria

• Active carious lesions
• Periodontal disease
• Fluorosis or enamel hypoplasia
• Current fluoride supplement use beyond standard toothpaste
• Pregnancy or lactation
• Systemic conditions affecting salivary flow

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B: Casein Phosphopeptide-Amorphous Calcium Phosphate	GC Tooth Mousse	In 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	Nano-Hydroxyapatite Gel	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.
Group D: Professional Fluoride Varnish	Sodium Fluoride varnish	Professional application of 5% sodium fluoride varnish (ProShield) applied to attachment margins at baseline and 3 months.

Primary Outcome Measures

Name	Time	Method
Change in Enamel Demineralization (DIAGNOdent values).	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.

Secondary Outcome Measures

Name	Time	Method
Temporal Changes in Enamel Mineralization	1 month (T1) and 3 months (T2)	Evaluation of DIAGNOdent values at intermediate time points to assess the progression or regression patterns (e.g., continuous improvement vs. biphasic response) of demineralization.

Trial Locations

Locations (1)

Bezmialem Vakif University, Faculty of Dentistry; Istanbul, Turkey (Türkiye)