PROJECT 2: INVISALIGN TRIAL

项目总结（项目2 -OI正畸试验） 我们以前的研究表明，大约80%的成骨不全患者， (OI)III型和IV型（中度至重度形式的OI）具有牙齿咬合不正。这是一个重大的未满足的 医疗需要，因为错牙合干扰了语言，咀嚼能力和对大脑的影响， 生活质量对于OI中的错牙合畸形，尚无循证治疗选择。在我们的临床实践中， 使用Invisalign®治疗了3例III型和IV型OI青少年的咬合不正，Invisalign®是一种广泛使用的FDA- 治疗咬合不正的获批方法（II类器械）。隐适美通常用于治疗青少年或 中等程度错牙合的年轻成人。错牙合畸形的严重程度可以用 同侪评估等级（PAR）评分。PAR评分介于15和40之间被认为是中等水平 严重性。我们建议进行一项多中心研究，以评估Invisalign治疗 骨性关节炎错牙合畸形的治疗。我们将在一个为期6个月的随机研究中评估错牙合畸形的改善情况。 研究，随后是一项开放标签扩展研究，评估完整的24个月Invisalign的结果 疗程目的1是确定使用Invisalign系统治疗6个月是否改善了 与未治疗的对照组相比（随机试验）。我们将招募具有OI类型的个人 年龄在12 - 40岁之间的III或IV级患者，患有中等严重程度的错牙合。将为受试者分配 治疗组接受隐适美治疗，对照组不接受正畸治疗 组）（每组n = 18）。随机化将根据OI类型、年龄和双膦酸盐进行分层 治疗状态主要终点为PAR评分的变化;次要终点包括 牙齿解剖运动假设是治疗会引起牙齿移动， 与对照组相比，平均PAR评分的下降幅度显著更大（表明错牙合畸形改善）。 本研究的目的2是确定Invisalign治疗的整个疗程是否改善口腔健康 相关生活质量（扩展研究）。在前6个月的随机治疗后，所有受试者将接受 Invisalign治疗。总治疗期将为24个月（+/- 6个月，基于达到 基线时规定的治疗目标）。主要研究终点将是口腔健康相关质量的变化 生命次要终点将是咀嚼的变化，在解剖学上表示为咬合的数量。 接触、咀嚼效率、功能参数以及患者满意度。这个假设是 口腔健康相关的生活质量和咀嚼能力将在Invisalign治疗过程中得到改善。这 这项研究将首次提供有关如何治疗咬合不正的科学证据。如果 成功的，这种方法可以迅速实施到临床实践中。

PROJECT SUMMARY (Project 2 – Orthodontic Trial in OI) Our previous studies have shown that approximately 80% of individuals with osteogenesis imperfecta (OI) type III and IV (the moderate to severe forms of OI) have dental malocclusion. This is a major unmet medical need as malocclusion interferes with speech, the ability to chew and detrimentally impacts on the quality of life. There are no evidence-based treatment options for malocclusion in OI. In our clinical practice we have treated malocclusion in 3 adolescents with OI types III and IV using Invisalign®, a widely used FDA- approved approach to treat malocclusion (Class II device). Invisalign is typically used to treat adolescents or young adults with malocclusion of intermediate severity. The severity of malocclusion can be determined using the Peer Assessment Rating (PAR) score. PAR scores between 15 and 40 are considered intermediate severity. We propose to perform a multicenter study to evaluate the efficacy and safety of Invisalign for the treatment of malocclusion in OI. We will assess the improvement in malocclusion in a 6-month randomized study, followed by an open-label extension study that evaluates the outcome of a full 24-months Invisalign treatment course. Aim 1 is to determine whether 6 months of treatment with the Invisalign system improves the malocclusion compared to an untreated control group (randomized trial). We will enroll individuals with OI type III or IV from 12 to 40 years of age who have malocclusion of intermediate severity. Subjects will be assigned to either receive Invisalign treatment (treatment group) or to be followed without orthodontic treatment (control group) (n = 18 per group). Randomization will be stratified according to OI type, age and bisphosphonate treatment status. The primary endpoint will be the change in PAR score; secondary endpoints will include anatomical tooth movement. The hypothesis is that the treatment will induce tooth movement and have a significantly larger decrease in mean PAR score (indicating improved malocclusion) than the control group. Aim 2 of the study is to determine whether a full treatment course of Invisalign treatment improves oral-health related quality of life (extension study). After the first 6 months of randomized therapy, all participants will have Invisalign treatment. The total treatment period will be 24 months (+/- 6 months, based on achieving the treatment goals specified at baseline). The primary study endpoint will be change in oral-health related quality of life. Secondary endpoints will be changes in mastication, expressed anatomically as the number of occlusal contacts, and masticatory efficiency, a functional parameter, as well as patient satisfaction. The hypothesis is that oral health-related quality of life and mastication will improve over the Invisalign treatment course. This study will provide for the first time scientific evidence on how to treat malocclusion in the context of OI. If successful, this approach can be rapidly implemented into clinical practice.