Trail design
This study is a parallel-group, randomized controlled, double-blinded clinical trial (Fig. 1). The protocol is following the CONSORT guidelines (2010)[14]. This trial will recruit orthodontic patients from the Department of orthodontics, Shanghai Stomatological Hospital. Clinical research coordinators will receive training on the design, methodology, clinical intervention, and keeping trial documentation of this study first. And then, they will explain the purpose and the arrangement of this study to the patients. The patients who are willing to participate in this study will be entered into the electronic data capture (EDC) system held on the computer server of Shanghai Stomatological Hospital.
Each participating patient will undergo the necessary medical examinations which include physical examinations, lateral cephalometry, Cone beam computed tomography (CBCT), and intra-oral scan. The participants will be randomly divided into two equal groups (PETG and TPU). Different tests of two groups (PETG and TPU) will be recorded before the treatment (M0), 12 weeks after treatment (M1). The procedure shows in Fig. 2.
Eligibility criteria
The patients will be assessed by orthodontists who have experience with clear aligners.
Inclusion criteria
The participants must meet the following criteria:
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Adult patients, aged 18-40years
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Permanent dentition, the first molar of the upper and lower and the anterior teeth are not missing
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The crowding of dentition ≥ 5mm, orthodontic treatment requires the extraction of the maxillary first premolar or the maxillary second premolar.
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Patients who are able to wear aligners as required time.
Exclusion criteria
The exclusion criteria of this study are as follows:
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Allergic to orthodontic thermoplastics
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Patients need to have orthognathic (jaw) surgery
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With symptoms or signs of temporomandibular joint disorders;
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With systemic diseases.
Interventions
All participants' maxillary first or second premolars will be selected at M0 to ensure that selected teeth can move towards the mesial or distal side 2mm and not be blocked out by adjacent teeth. A series of 10 maxillary clear aligners were programmed to accomplish the movements from M0 to M1, and the increments of movement of the maxillary premolar will be designed as 0.2mm in each step. The type of orthodontic thermoplastic for aligners manufactured depends on the card of their envelopes, PETG (Scheu, Iserlohn, Germany) or TPU (Maxflex, Taiwan). The clear aligners will be collected at the end of the fifth and tenth weeks. The patients will take an intra-oral scan at the same time. Routine follow-up will be conducted 2 weeks after programmed 10 steps.
The process and critical nodes of interventions in this study were showed in Fig. 2. The flow charts were printed and delivered to clinical doctors for reminders. In the first stage, from M0 to M1, the programmed movements were designed under the discussion of specialists.
Patient and public involvement
The patients and the public will not be involved in the design, conduct, reporting or dissemination plans in this trial.
Outcome measures
The records of patients will be anonymized before analysis to eliminate analyst bias.
Primary outcome
The primary outcome will be the efficiency of clear aligners on OTM. Intra-oral scan (iTero, Align Technology, San Jose, Calif) will be collected in the key steps as shown in Fig. 2. The intra-scan digital models of different time points will be superimposed in the Rapidform2006 (INUS Technology Inc., Seoul, Korea) for measurements (Fig. 3). Landmarks' three-dimensional coordinates in the buccal side(A1-A4, B1-B4) of the maxillary premolars will be recorded to calculate the crowns’ movements, including mesial tipping, distal tipping, bucalinclination, lingual inclination, rotation, intrusion, and extrusion.
Secondary outcomes
The CBCT images of different time points will be saved as Digital Imaging and Communications in Medicine (DICOM) format files and imported into Dolphin software (Dolphin Imaging & Management Solutions Corporation, Chatsworth, CA, USA) for superimposition based on voxel (Fig. 3.). The roots’ movements and the rotation angle will be inferred through the point marked (C1-C4, D1-D2). The lengths of the roots and crowns will also be measured (h1, h2) (Fig. 4). The efficiency will finally be calculated with the ratio of clinical tooth movements and designed movements. Correlations between age and OTM, as well as between gender and OTM, will be analysed.
Target sample size
The sample size was calculated using PASS software (Utah, USA) in this trial. The expectation hypothesis is that TPU orthodontic thermoplastics will increase the efficacy of orthodontic tooth movement (OTM). The studies of Justin [3]and Susan et al.[2] were used to estimate standard deviation. The sample size of 20 patients in a single group will achieve 80% power to detect a difference in 10 weeks with a 0.05 two-sided significance level. Considering a 10% dropout rate, this trial will recruit a total of 44 patients.
Participant recruitment
Patients will be recruited at the orthodontic department in Shanghai Stomatological Hospital from 1 June 2023 to 31 December 2024 (anticipated). The notification will be published on the official website and hospital. The patients will be assessed by their orthodontists whether meet the inclusion criteria. The patients invited will have at least two weeks to make a decision.
Sequence generation and randomization
Block randomization was used in this study. The subjects who met the criteria were randomly assigned to the experimental group and the control group according to the ratio of 1:1. A random allocation table was generated by an independent statistician through SAS 9.4 (SAS Institute Inc., Cary, NC, USA) software. Randomization allocation and masking were achieved by the envelope method.
Participant allocation
In this study, patients’ allocation will be accomplished by numbered, opaque, sealed envelopes. The envelopes will be kept by the dental technician in charge of aligner manufacture. After the orthodontic design is confirmed, the dental technician will open the allocation envelope to identify the type of orthodontic thermoplastics. The allocation envelope will only be opened when clear aligners need to be manufactured.
Blinding
This study is a double-blinded clinical trial (Fig. 5). The nurse collects the digital model registered with a study number and submits it to the dental technicians. The dental technicians will know and keep the group allocation when the corresponding envelope is open before manufacture. Then, unaware of the group allocation, the nurse receives the clear aligners with the study number. Because of the similar transparency and elasticity, clear aligners made of PETG and TPU are hard to distinguish. Thus, the orthodontists and patients only know the study number and are blinded for group allocation. The group allocation and patients' information will be blinded to the analyst at the analyzing stage.
Data collection and management
Plans for data and records collected
The data will be recorded in case report forms (CRFs) designed by specialists and Zhejiang Taimei Technology Co., Ltd. The CRF will be filled out for each patient by coordinators. The fixed period of supervision will be taken by a qualified clinical research assistant. The clinical research assistant is blinded to the group allocation and reviews this trial's informed consent and CRFs. The original CRFs will be saved in the data management center of Shanghai Stomatological Hospital.
Data management
All patients’ image data, questionnaires, and measurements will be collected and checked regularly. The primary data will be coded to allow for the blinding of the analyst. The coded data will be exported into SPSS 24.0 (Chicago, the United States) for further analysis when the trial is accomplished.
Post-trial care
All files of this trial will be retained for at least ten years at the end of the study.
Confidentiality
All patients' data will be securely stored with limited access. All participants will be informed that their records will have the possibility to be reviewed by the sponsor, the research Ethics Committee (EC), and the regulatory authority. All unpublished results and records will be deemed confidential. Any published reports will not contain personal data for the protection of personal privacy.
Statistical methods
Statistical methods for outcomes
The primary and secondary outcomes are continuous variables. Descriptive statistics will be first used to summarize the outcomes of the study and show the distribution, mean differences, and standard deviations of the data. Spearman correlation was used to test for correlation between age/gender and the efficiency of OTM. The statistical analysis of the efficiency will be performed through the one-way ANOVA test. It will be considered significant when P < 0.05.
Methods to handle missing data
The Multiple Imputation (MI) method will be used to deal with missing data.
Oversight and Monitoring
Trial Monitoring Committee
The Trial Monitoring Committee will consist of three experienced orthodontists. The committee will meet every 4 weeks to ensure the trial is being carried out under good clinical practice (GCP). All adverse events from M0 to M1 will be recorded and reported to the committee. The committee will assess and manage the adverse events. Patients have the right to quit the study or defer to the committee. The committee will decide whether the patient needs to leave when adverse events occur. The status of the leaved patient will be followed up.
Plans for communicating important protocol amendments
Any revisions during the trial need to be reported to the research ethics committee and take permission. The informed consent will be rewritten in accordance with the modifications and re-signed with patients.
Dissemination and publication
The data of the current study will be analyzed and performed a summary report. The final report will be published in orthodontic journals by the principal researcher.