Clear Aligners for Misaligned Teeth in Osteogenesis Imperfecta

Recruiting at 3 trial locations

Overseen By Dianne Nguyen

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: Bisphosphonates

Must not be taking: Growth hormone, Corticosteroids, Thyroid hormones

Disqualifiers: Prior orthodontics, Impacted teeth, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 24 months

57 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that affect bone metabolism, except for bisphosphonates.

What data supports the effectiveness of the treatment Invisalign, Clear Aligners, Invisalign for misaligned teeth in Osteogenesis Imperfecta?

Research shows that Invisalign clear aligners are effective in improving dental alignment in various conditions, such as correcting deep overbites and leveling the curve of Spee, which suggests they may also help with misaligned teeth in Osteogenesis Imperfecta. ^{1 2 3 4 5}

Are clear aligners generally safe for humans?

Clear aligners, like Invisalign, are generally safe but can cause some issues such as bite problems, pain, and gum disease, especially if used without dental supervision. It's important to have a dentist or orthodontist involved in the treatment to minimize these risks. ^{6 7 8 9 10}

How does the treatment Invisalign differ from other treatments for misaligned teeth in osteogenesis imperfecta?

Invisalign, or clear aligners, offers a unique approach by using removable, transparent trays to gradually adjust teeth alignment, which is different from traditional braces that use fixed metal brackets and wires. This method allows for more comfortable and aesthetic treatment, and its digital planning can be tailored to the specific needs of patients with osteogenesis imperfecta, who may have unique dental and skeletal challenges. ^{10 11 12 13 14}

Research Team

Julia Cohen-Levy

Principal Investigator

McGill University

Deborah Krakow, M.D.

Principal Investigator

University of California, Los Angeles

Jean-Marc Retrouvey

Principal Investigator

Baylor College of Medicine

Janice Lee

Principal Investigator

NIDCR/NIH

Eligibility Criteria

This trial is for individuals aged 12-40 with Osteogenesis Imperfecta types III or IV and mild to moderate misaligned teeth, who haven't had previous orthodontic treatments like braces. Participants must have enough intact teeth for the treatment and cannot be pregnant or on certain medications affecting bone metabolism.

Inclusion Criteria

I am between 12 and 40 years old.

I have been diagnosed with Osteogenesis Imperfecta type III or IV.

Malocclusion of intermediate severity defined as a PAR score between 15 and 40

Exclusion Criteria

I do not have severe gum disease, active periodontal disease, or cancer that could affect orthodontic treatment.

Pregnancy - positive during screening visit.

I have teeth that haven't come in or are stuck.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Initial observation period before orthodontic treatment begins

4 months

1 visit (in-person)

Treatment

Participants receive orthodontic treatment using Invisalign clear aligners

24 months

12 visits (in-person, every two months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• Invisalign

Trial Overview The study tests Invisalign clear aligners' effectiveness and safety in treating dental malocclusion in people with Osteogenesis Imperfecta. It's a less invasive alternative to braces, conducted at McGill University, UCLA, and NIDCR aiming to establish treatment guidelines.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Subjects with a PAR score between 15 and 50 and fulfilling the other eligibility criteria will be offered participation in the trial.

Group II: Natural History Active Control 1 Intervention

Subjects with a PAR score outside of 15-50 will be offered the opportunity to remain on study for the Natural History arm.

Invisalign is already approved in United States, Canada for the following indications:

Approved in United States as Invisalign for:

• Orthodontic treatment for malocclusion in patients with Osteogenesis Imperfecta

Approved in Canada as Invisalign for:

• Orthodontic treatment for malocclusion in patients with Osteogenesis Imperfecta

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

University of Missouri, Kansas City

Collaborator

Trials

73

Recruited

34,600+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

In a study of 40 skeletal Class II patients treated with Invisalign® Mandibular Advancement, significant improvements in dental and skeletal measurements were observed, particularly in prepubertal (CVM2) and pubertal (CVM3) stages.

The treatment was effective in producing skeletal changes during the pubertal stage, with an annual growth rate of 5.8 mm, while prepubertal treatment mainly resulted in dentoalveolar changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short term dentoskeletal effects of mandibular advancement clear aligners in Class II growing patients. A prospective controlled study according to STROBE Guidelines. Ravera, S., Castroflorio, T., Galati, F., et al.[2021]

In a study involving 152 adult orthodontic patients, both Invisalign and braces showed overall improvement in treatment outcomes, indicating that both methods are effective for correcting malocclusions.

However, while both treatments were successful, Invisalign had lower scores than braces in specific areas like buccolingual inclination and occlusal contacts, suggesting that traditional braces may provide more precise adjustments in these aspects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of the Invisalign appliance in extraction cases using the the ABO model grading system: a multicenter randomized controlled trial. Li, W., Wang, S., Zhang, Y.[2020]

Both traditional fixed appliances and Invisalign clear aligners effectively level the curve of Spee in patients with increased COS depth, as shown in a study involving 62 subjects (30 treated with Invisalign and 32 with fixed appliances).

The study found that while fixed appliances caused extrusion of posterior teeth and flaring of mandibular incisors, Invisalign allowed for significant intrusion of mandibular incisors with better control over their inclination, suggesting different mechanisms of action between the two treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leveling the curve of Spee: Comparison between continuous archwire treatment and Invisalign system: A retrospective study. Rozzi, M., Tiberti, G., Mucedero, M., et al.[2023]

In a study comparing 58 patients, traditional fixed appliances showed better outcomes in six smile-related variables compared to Invisalign clear aligners, indicating that fixed appliances may be more effective for certain smile improvements.

Invisalign did perform better in adjusting maxillary incisor position and inclination, but overall, traditional braces had a greater impact on the overall smile aesthetics for patients with Class I nonextraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smile outcome comparison of Invisalign and traditional fixed-appliance treatment: A case-control study. Christou, T., Abarca, R., Christou, V., et al.[2020]

In a study of 48 adults with skeletal deep bites, both the Invisalign G5 protocol and full fixed appliances (FFA) effectively reduced overbite and improved skeletal measurements, indicating their efficacy in treating this dental issue.

While both treatments were effective, the FFA group showed greater skeletal changes compared to the Invisalign group, suggesting that traditional braces may provide more significant skeletal adjustments in deep bite cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Invisalign (G5) with virtual bite ramps for skeletal deep overbite malocclusion correction in adults. Henick, D., Dayan, W., Dunford, R., et al.[2021]

A review of the FDA's MAUDE database revealed 104 adverse events associated with direct-to-consumer (DTC) sequential aligners, highlighting significant oral health issues such as bite problems (41.3%), orofacial pain (29.8%), and periodontal complications (26.6%).

The majority of patients (69.2%) sought follow-up care from dentists not affiliated with the DTC aligners, indicating that the lack of professional supervision during treatment can lead to serious and potentially irreversible dental problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Direct-To-Consumer Sequential Aligners-A Study of the MAUDE Database. Belgal, P., Mhay, S., Patel, V., et al.[2023]

A retrospective analysis of 173 medical device reports related to the Invisalign system revealed that 97.7% were adverse events, with 26% classified as serious or life-threatening, highlighting potential safety concerns associated with its use.

The most common serious adverse events included difficulty breathing, anaphylaxis, and throat swelling, indicating that healthcare providers should be vigilant and prepared to manage these reactions in patients using Invisalign.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse clinical events reported during Invisalign treatment: Analysis of the MAUDE database. Allareddy, V., Nalliah, R., Lee, MK., et al.[2017]

Over a 5-year period, 175 adverse events and reactions (AERs) related to sequential aligners were reported in the FDA's MAUDE database, with a significant portion (73.71%) being mandatory reports from manufacturers.

Common AERs included allergic reactions (18.29%), with serious cases such as anaphylaxis (11.43%) and angioedema (2.29%), as well as other issues like gastrointestinal problems and neuromuscular symptoms, highlighting the need for awareness of potential risks associated with sequential aligner use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of adverse events with use of orthodontic sequential aligners as reported in the manufacturer and user facility device experience database. Thavarajah, R., Thennukonda, RA.[2017]

A study evaluated the cytotoxicity of four clear aligner systems (Invisalign, Eon, SureSmile, and Clarity) by immersing them in saline for one month and testing their effects on gingival fibroblasts, revealing that all systems exhibited some level of toxicity.

Among the systems tested, Clarity showed the lowest toxicity at various concentrations, although all aligners demonstrated statistically significant differences in cell viability compared to the control, indicating slight to moderate toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity assessment of different clear aligner systems: An in vitro study. Alhendi, A., Khounganian, R., Almudhi, A.[2022]

In a study of 45 adult patients with anterior open bite, clear aligners effectively closed the bite by causing significant extrusion of the upper and lower incisors and intrusion of the upper and lower molars.

The treatment resulted in notable retraction of both maxillary and mandibular incisors, demonstrating that clear aligners can successfully manage the vertical dimension in patients with open bite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of open bite closure using clear aligners: a retrospective study. Harris, K., Ojima, K., Dan, C., et al.[2020]

Aligners can effectively treat anterior spaces caused by periodontal diseases without causing damage to periodontal tissues, as observed in a study of seven patients.

No significant changes were noted in periodontal health indicators, such as bleeding on probing and probing depth, before and after treatment, indicating the safety of using aligners in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patients with anterior spaces caused by periodontal disease treated with aligner technique]. Bai, YX., Yang, B., Dai, Q., et al.[2009]

Clear aligner treatment has expanded its use from just correcting crowding or spacing to addressing moderate malocclusions, including both extraction and non-extraction cases, due to advancements in biomaterials and biomechanics.

Orthodontists must understand the strengths and limitations of clear aligners, particularly in three-dimensional tooth movement control, and should actively modify digital treatment plans based on their clinical experience to optimize outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advantages and disadvantages of clear aligner treatment in orthodontics]. Liu, Y.[2018]

A study of 27 individuals with osteogenesis imperfecta revealed a negative overjet in 6 participants, indicating potential dental alignment issues.

The findings suggest that individuals with osteogenesis imperfecta may be at a higher risk for developing malocclusion due to skeletal discrepancies that are partially compensated by incisor inclination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incisor and jaw relationship in 27 persons with osteogenesis imperfecta. Stenvik, A., Larheim, TA., Storhaug, K.[2022]

Clear aligners (Invisalign) can effectively treat unilateral canine crossbites, providing a non-invasive option for correction.

Combining clear aligners with partial fixed appliances and removable elastics can enhance treatment outcomes by allowing for protected movement during the correction process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unilateral canine crossbite correction in adults using the Invisalign method: a case report. Giancotti, A., Mampieri, G.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Short term dentoskeletal effects of mandibular advancement clear aligners in Class II growing patients. A prospective controlled study according to STROBE Guidelines. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The effectiveness of the Invisalign appliance in extraction cases using the the ABO model grading system: a multicenter randomized controlled trial. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Leveling the curve of Spee: Comparison between continuous archwire treatment and Invisalign system: A retrospective study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Smile outcome comparison of Invisalign and traditional fixed-appliance treatment: A case-control study. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of Invisalign (G5) with virtual bite ramps for skeletal deep overbite malocclusion correction in adults. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Direct-To-Consumer Sequential Aligners-A Study of the MAUDE Database. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Adverse clinical events reported during Invisalign treatment: Analysis of the MAUDE database. [2017]

8. India pubmed.ncbi.nlm.nih.gov

Analysis of adverse events with use of orthodontic sequential aligners as reported in the manufacturer and user facility device experience database. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Cytotoxicity assessment of different clear aligner systems: An in vitro study. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of open bite closure using clear aligners: a retrospective study. [2020]

11. China pubmed.ncbi.nlm.nih.gov

[Patients with anterior spaces caused by periodontal disease treated with aligner technique]. [2009]

12. China pubmed.ncbi.nlm.nih.gov

[Advantages and disadvantages of clear aligner treatment in orthodontics]. [2018]

13. Denmark pubmed.ncbi.nlm.nih.gov

Incisor and jaw relationship in 27 persons with osteogenesis imperfecta. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Unilateral canine crossbite correction in adults using the Invisalign method: a case report. [2018]