Clear Aligners for the Treatment of Dental Malocclusion in OI

Study Overview
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Brief Summary
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Misalignment of teeth and jaws (also called malocclusion) is a common life altering problem facing many individuals with Osteogenesis Imperfecta (OI). The presence of Dentinogenesis Imperfecta in teeth of OI individuals makes the use of conventional orthodontics in the form of braces very challenging. Clear aligners are newer form of orthodontic treatment and is less invasive than braces. Therefore, the aim of our study is to evaluate the efficiency and safety of using Invisalign clear aligners for orthodontic treatment in individuals with Osteogenesis Imperfecta. We seek individual with Osteogenesis Imperfecta, with mild to moderate malocclusion and no prior history of orthodontic treatment. This study will be held at three sites - McGill University, University of California Los Angeles and National Institute of Dental and Craniofacial research. This study will for the first time, help define guidelines for safe and efficient orthodontic treatment using clear aligners in individuals with Osteogenesis Imperfecta. If successful, this approach can rapidly be implemented into clinical practice, as the Invisalign system is readily available to orthodontists.

Detailed Description
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Osteogenesis imperfecta (OI) is a heritable connective tissue disorder leading to frequent fractures and bone deformities. In about 90% of individuals with OI, the disease is caused by dominant mutations in one of the two genes coding for collagen type I, COL1A1 and COL1A2. The phenotype of OI ranges widely, which is captured by the Sillence classification of OI into clinical types I through IV. Individuals who have bone disease that is severe enough to lead to long-bone deformities, such as bowing of femurs and tibias, are usually diagnosed with OI type III (severe bone fragility) or IV (moderate bone fragility). Apart from the well-known features of OI in the extracranial skeleton, OI is frequently associated with dental and craniofacial issues. These abnormalities are a source of major concern to patients. Misalignment of the jaws is a common problem in individuals with OI Type III and IV. Malocclusion associated with OI types III and IV differs markedly from the types of malocclusion commonly observed in the general population. Malocclusion in the general population is predominantly class II, however, OI types III and IV are commonly associated with class III malocclusion. The Invisalign® system (Align Technology, Santa Clara, CA) is a personalized and FDA-approved (Class II device; 510(k) number: K143630) approach to treat malocclusion. It involves incrementally moving teeth with a series of removable, custom-made clear polyurethane trays (aligners) that exert forces on teeth. The aligners are transparent ('clear aligners') and therefore are less visible than traditional braces that are made of metal. An important consideration in the treatment of patients with OI is that Invisalign does not require surface etching and cement bonding of metal braces to the tooth surface, which is difficult in the presence of dentinogenesis imperfecta. In this study, we will therefore use the Invisalign system to treat malocclusion associated with OI. This study will directly inform clinical orthodontic practice in an area of unmet clinical need and utilizes a treatment method that may be immediately implemented. Individuals who meet the eligibility criteria will be able to enroll in the intervention arm of the study to undergo orthodontic treatment. Participants who fail to meet the eligibility criteria will be offered to participate in the study for observation purposes (natural history arm) without undergoing treatment. Participants in the intervention arm will need to visit the study site every two months for the study duration (28 months). Initial four months will involve observation period followed by two years of orthodontic treatment. Participants in the natural history arm will visit the study site every six months for a period of two years (4 visits). A complete oral exam, craniofacial evaluation, intra-oral photos, intra-oral scans, face photos, masticatory test, cone-beam CT and self-reported questionnaires will be done during the visits.

Official Title
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Use of Clear Aligners for the Treatment of Dental Malocclusion in Individuals With Osteogenesis Imperfecta

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Device: Invisalign


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of OI. Malocclusion of intermediate severity defined as a PAR score between 15 and 50. Age range 12 to 40 years at the screening visit. Presence of minimum number of intact teeth to proceed with orthodontic treatment. Exclusion Criteria: Prior orthodontic treatment defined as - any history of braces, palatal expansion or Invisalign treatment. Candidates who meet the PAR score but need surgical intervention for correction of malocclusion Presence of impacted or retained teeth. Use of medication, other than bisphosphonates, known to affect bone metabolism and contraindicated on orthodontic treatment, examples are, growth hormone, corticosteroids (chronic use) and thyroid hormones. Presence of other dental, oral or systemic conditions that may interfere with orthodontic treatment. Examples are severe gingivitis, active periodontal disease, cancer. Pregnancy - positive during screening visit.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Subjects with a PAR score between 15 and 50 and fulfilling the other eligibility criteria will be offered participation in the trial. | Device: Invisalign<br>* Invisalign clear aligner system<br>|
| No Intervention: Natural History<br>Subjects with a PAR score outside of 15-50 will be offered the opportunity to remain on study for the Natural History arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peer Assessment Rating score (PAR) | The Peer Assessment Rating (PAR) index is a valid and reliable measure of orthodontic treatment outcome and is the most widely accepted such index. A score of zero represents an ideal occlusion and in general the higher the score, the more extensive the malocclusion. | Day 0, Every two months up to 28 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tooth movement | Change from baseline in anatomical tooth movement at each post-baseline time point | Every two months from baseline up to 24 months |