Trial design and study registration

This is an open-label, 2-arm, parallel randomized controlled trial. The protocol followed guidance from the Consolidated Standards of Reporting Trials guidelines. The study protocol was approved by the Institutional Ethics Committee (Città della Salute e della Scienza di Torino, approval no. 0006323) of the coordinating center. It was performed according to the Declaration of Helsinki, with pertinent national and international regulatory requirements. The trial was registered at the ClinicalTrial.gov Web site ( ClinicalTrials.gov registration no. NCT04760535). The Protocol Registration System was used to upload and update data on the controlled trial.

Participants and study setting

In this study, patients referred to the Department of Orthodontics of the University of Turin, Turin, Italy (coordinating center) and to the private practice of the authors were recruited from January 2020 to January 2021.

All authors are orthodontists who routinely conduct cephalometric radiographs before and after treatment. They possess the capability to collect intraoral scans and affirm that their practice can dedicate sufficient time to patient scheduling to allow focused recording of all data required for the study. Furthermore, they did not anticipate retiring, selling the practice, or relocating during the study period. Signed, written informed consent was a prerequisite for inclusion in the trial.

The inclusion criteria were as follows: (1) patients with a posterior transverse interarch discrepancy of a maximum of 6 mm; (2) mixed dentition phase with CVMS <3; (3) fully erupted maxillary and mandibular first molars; (4) maxillary second premolar cusps positioned apically to the half pulp chamber line of the ipsilateral maxillary first permanent molars on pretreatment panoramic radiographs, indicating that the deciduous molars can serve as secure anchoring teeth for a minimum of 12 months; and (5) good general health, according to medical history and clinical judgment. Subjects with craniofacial malformations (including cleft lip or palate), a history of dental trauma, oral neoformations, and other oral cavity pathologies, or previous or concurrent orthodontic treatment were excluded from the study.

The posterior transverse discrepancy between the maxillary and mandibular arches was determined on the basis of the difference between the maxillary intermolar width (distance between the central fossae of the maxillary first molars) and the mandibular intermolar width (distance between the mesiobuccal cusps of the first mandibular molars). All participants provided written informed consent and could withdraw from the study at any time.

Intervention

Subjects assigned to the CAT group underwent Invisalign First Phase I treatment (Align Technology, Inc, Santa Clara, Calif). The Invisalign First aligners were fabricated in a multilayer aromatic thermoplastic polyurethane/co-polyester 0.75 mm (0.030-in)-thick with a fine 3D manufacturing process. Subjects in this group were instructed to wear aligners 22-24 h/d for the entire duration of the therapy. They were asked to remove their aligners only while eating, drinking (except water), or cleaning.

The ClinCheck software (Align Technology, Inc) was used to plan orthodontic movements. Regarding staging, permanent molars moved buccally first, using the rest of the arch as anchorage. When they reached their final position, the deciduous molars and canines moved buccally using permanent molars and incisors as anchorage units. Because of the short clinical crowns of deciduous teeth, specific attachment shapes were designed to increase aligner retention and control the tipping movement (to obtain torque compensation and to avoid a deepening of the curve of Wilson). ^, The expansion was planned with a request for 0.15 mm of extrusion plus 2° of additional buccal root torque for each stage, performed until the palatal cusp tip of the posterior maxillary teeth contacted the buccal cusp tip of the mandibular posterior teeth. Patients wearing Invisalign First were also asked to complete an aligner wear chart. The self-reported compliance levels were categorized as follows: compliant (reported wear of aligners as advised), partially compliant (aligners wear instructions not followed precisely), and noncompliant (not wearing aligners). Maxillary and mandibular vacuum-formed retainers (Essix C+; Dentsply Sirona, Charlotte, NC) were produced using an Erkoform thermoforming machine (Erkodent, Pfalzgrafenweiler, Germany). The retainers were trimmed to cover the palatal surface and all fully erupted teeth and extended halfway across the occlusal surface of the most distal molar. Participants were instructed to wear their retainers exclusively during the night, adhering to a nightly routine. After the delivery of the retainers, thorough oral hygiene instructions were conveyed through written and verbal communication.

Subjects assigned to the RME group underwent RME using a tooth-borne Hyrax-type appliance. The Hyrax-type maxillary expander is a tooth-borne expansion appliance that is fixed to the maxillary second deciduous molars using bands and includes a midline 12-mm self-locking screw (0.9 mm, complete turn; Forestadent, Pforzheim, Germany). The expansion screw was connected to the conventional molar bands or printed clasps, which were modeled surrounding the molars via a 0.9-mm stainless steel wire framework. The framework was soldered to the bands and extended on the palatal side to the deciduous canines. A qualified laboratory technician fabricated the expander. The Hyrax-type maxillary expander was bonded to the teeth with an orthodontic band composite (Transbond Plus Light Cure Band Adhesive; 3M Unitek, Monrovia, Calif) and light-cured using a halogen lamp (Optilux, Kerr, Orange, Calif) for 20 seconds per tooth.

The expansion protocol was one quarter-turn twice a day (0.45 mm activation per day) until overcorrection with the maxillary lingual cusps in contact with the mandibular buccal cusps.

When an increase in the mandibular anterior arch perimeter or a curve of Wilson flattering was requested, a removable mandibular Schwarz appliance was used for mandibular “dental decompensation” The Schwarz appliance was an acrylic horseshoe-shaped appliance that fitted along the lingual border of the mandibular dentition, extending distally to the permanent first molars. It included a midline 9-mm self-locking screw (Forestadent, Pforzheim, Germany; 0.9 mm, complete turn), and the connection with the mandibular second deciduous molars was ensured by ball clamps at their interproximal undercut. A qualified laboratory technician fabricated it. The expansion protocol for mandibular appliances was one quarter-turn a week with full-time wear. The expander was left passively for retention for a minimum of 6 months, and the Schwarz appliance continued to be worn full-time as a passive retainer until the maxillary expander was removed. At the time of appliance delivery, written and verbal oral hygiene instructions, including cleaning methods, were provided. In addition, written informed consent was obtained from each patient or the parents.

In both intervention groups, the amount of expansion was determined individually, depending on the severity of maxillary arch constriction. In case of breaking or losing the appliances, the patients were asked to visit the Orthodontic Department or private practice of the authors as soon as possible.

For all patients, full mouth intraoral scans were obtained using an intraoral scanner (iTero Element; Align Technology, Inc) before appliance placement (T0) and at the end of the retention period/treatment (T1), when the appliances were removed.

Randomization

Patients who fulfilled the eligibility criteria were enrolled and randomly allocated into the 2 groups using the Microsoft Excel (Microsoft, Redmond, Wash) random number generator.

The CAT group comprised patients who underwent Invisalign First Phase I treatment (Align Technology, Inc), and the RME group comprised patients who underwent RME treatment with a tooth-borne Hyrax-type appliance.

Outcomes

The stereolithographic (STL) files obtained from the scanner were imported into the reverse modeling software package Geomagic Control X (3D Systems Inc, Rock Hill, SC) to perform all measurements by 2 operators (M.F. and V.G.). Each study cast scan was manually preprocessed to remove unwanted data artifacts from the analysis.

The primary outcome was to evaluate changes in palatal morphology, defined as variations in palatal volume. The palatal surface area and volume were calculated from digitized study models within the boundaries of the palate by creating mutually perpendicular median sagittal, distal, and gingival planes ( Figs 1 and 2 ).

Definition of palatal boundaries on digital models: A, Distal plane: passing through points A and B; B, Sagittal plane: passing through points C and D; C, Gingival plane: passing through points A, B, and C by connecting the midpoints of the dentogingival junction of all primary teeth. Point A , distal of the permanent maxillary right first molar; Point B , distal of the permanent maxillary left first molar; Point C , at the center of incisive papilla; Point D , in the middle between points A and B).

Schematic representation of: A , Palatal surface area; B, Palatal volume on digital models.

Then, intermolar and intercanine transverse widths at the cusp and gingival level were measured: the maxillary intercanine width at the cusp level was defined as the distance between the cusp tips of the maxillary right and left canines; the maxillary intermolar width at the cusp level was defined as the distance between the mesiobuccal cusp tips of the maxillary right and left first molars; the maxillary intercanine at the gingival level was defined as the distance between the midpoints of the palatal dentogingival junction of the maxillary right and left canines; and the maxillary intermolar width at the gingival level was defined as the distance between the midpoints of the palatal dentogingival junction of the maxillary right and left first molars ( Fig 3 ). The 2 observers (M.F. and V.G.) performed all measurements 3 times.

Intercanine and intermolar maxillary arch widths assessed at the cusp level ( blue ) and gingival level ( red ) on digital models.

Blinding

Patients and interventionists were not blinded because of the nature of the intervention. The trial adhered to established procedures to maintain separation between staff taking outcome measurements and delivering the intervention, ensuring that those who conducted and evaluated measurements differed from the interventionists. Both interventionists and participants and outcome assessors were blinded to the group assignment. Interventionists and participants were blinded to outcome measurements and trial results throughout the study. Only outcome assessors were not blinded to outcome measurements and trial results.

Sample size and statistical analysis

The sample size was calculated based on the primary objective of comparing palatal volume changes between the two groups. Using the software G∗ Power (version 3.1; Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany), an a priori sample size calculation was conducted to ensure adequate power for detecting clinically meaningful differences between the groups, based on data from a previous study evaluating similar outcomes in comparable patient populations.

Considering an expected effect size of 1.0, a minimum of 17 subjects per group was necessary to achieve a power of 0.80 with an alpha level set at 0.05. To account for a potential dropout rate of approximately 10%, the resulting sample size for each group was 20 subjects.

Univariate and bivariate descriptive statistics for categorical variables were described as relative/absolute frequencies, whereas continuous variables were described as mean and standard deviation. Bivariate descriptive statistics for continuous variables were estimated for the whole cohort or stratified by the group (CAT and RME) and the T0 vs T1 measurements. The Shapiro-Wilk test and the skewness and kurtosis test were performed to verify the distribution of continuous variables, considering P <0.05 for significance. A Fisher’s exact test was performed to assess the comparability of gender distribution between the two intervention groups. The paired t-test assessed the intragroup differences for all parameters from T0 to T1 in both groups and the indipendent samples t-test for the intergroup differences among T0-T1 variation. All reported P values were obtained from the 2-sided exact method at the conventional 5% significance level.

The intraclass correlation coefficient (ICC) was calculated to assess intrarater and interrater reliability.

For intrarater reliability, measurements for intercanine width, intermolar width, palatal surface, and palatal volume were conducted by 1 investigator (V.G.) using a specified approach detailed in the outcome subparagraph. The same investigator (V.G.) then repeated all measurements after a 4-week interval to evaluate the consistency of the assessments. For interrater reliability, a different investigator (M.F.) applied the same standardized procedure to assess intercanine width, intermolar width, palatal surface, and palatal volume.

Data were analyzed using Stata software (version 17; StataCorp LLC, College Station, Tex), which was also used for chart making.