Accelerated Invisalign Therapy in Conjunction With Acceledent Aura

Study Overview
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Brief Summary
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Purpose: The objective of this study is to investigate the effects of accelerated Invisalign and vibration therapy on rate of orthodontic tooth movement, activation of inflammation biomarkers as well as pain levels experienced by orthodontic patients during the initial 12 weeks of alignment. Participants: Up to 30 orthodontic patients of the University of North Carolina Orthodontic Residency Program will be recruited for this study. Patients older than 18 years old will be otherwise healthy subjects previously diagnosed with malocclusion. Procedures (methods): Each patient will be randomly allocated into either a control group or one of two intervention groups. Patients within the control group will receive standard Invisalign therapy without vibration. Patients within the intervention groups will receive accelerated Invisalign therapy with or without vibration. Patients receiving vibration therapy will utilize an AcceleDent Aura device which provides a light vibration at .25 Newtons (N) and 30 Hertz (Hz) frequency for twenty minutes daily. Three dimensional images of each subject's dentition will be recorded five times at 0 days, 4 days, 2 weeks, 6 weeks, and 12 weeks progress visits.

Detailed Description
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Align Technology©, Inc. developed Invisalign® in 1997 to meet the esthetic demands of orthodontic patients and providers. Invisalign patients receive a series of computer-assisted designed stereolithic clear retainers to incrementally resolve their malocclusion. Invisalign® and other advances in orthodontic technology such as clear aligners, ceramic brackets and lingual braces offer options to address the esthetic demands of most orthodontic patients but duration of treatment continues to be one of the most challenging aspects of practice. In 2008, OrthoAccel Technologies©, Inc. developed the AcceleDent device to accelerate tooth movement and reduce orthodontic treatment time. Patients receiving vibration therapy are instructed to bite down on the AcceleDent mouthpiece, which vibrates at a .25 N (25 grams) force level with a 30 Hz frequency for 20 minutes per day. The theory underlying AcceleDent and the use of vibration to expedite orthodontic tooth movement started in 1892 with the studies of Julius Wolff, who discovered bone adapts to pressure loads. In 2001, Astronauts in space attempted to use the principles of Wolff's Law to maintain normal bone quality by working out and performing daily tasks while standing on a vibrating plate with the aid of elastic straps. In 2004, the effect of vibration therapy on bone density was further supported when increased bone density and strength was noted in post-menopausal women who received whole body vibration therapy. OrthoAccel claims vibration therapy using the AcceleDent device can reduce treatment time up to 50 percent by accelerating the process of bone remodeling required for orthodontic tooth movement. In 2013, despite relatively little scientific evidence, the US Food and Drug Administration (FDA) approved AcceleDent as a class II medical device and orthodontic accessory to facilitate accelerated tooth movement. Invisalign therapy in conjunction with AcceleDent has been aggressively marketed towards the esthetically sensitive patient who, not so coincidentally, is the most concerned with duration of treatment. Some orthodontic providers using vibration therapy have deviated from the standard 2-week aligner schedule and recommend a 4-day aligner schedule. Orthodontic patients receiving accelerated Invisalign therapy in conjunction with AcceleDent claim reduced treatment time by as much as 50 percent. What is responsible for the positive results? The accelerated tooth movement might simply be the result of the accelerated Invisalign therapy, which would raise the question of whether vibration therapy and the cost associated with AcceleDent is justified. The purpose and primary specific aim of our study will be to determine the cause of the accelerated tooth movement. Because the vibration therapy is used in conjunction with an accelerated Invisalign aligner schedule, there is an assumption that the vibration therapy is promoting faster tooth movement. However, the current literature, from clinical trials, supporting the efficacy of vibration therapy on accelerated tooth movement is lacking. Accelerated orthodontic tooth movement may offer many benefits to both, the patient and the orthodontist. Reduced treatment time reduces the burden of orthodontic treatment by decreasing risk for undesired treatment sequelae (e.g., white spot lesion, caries, gingivitis, etc) and potentially reduces the discomfort commonly associated with orthodontic treatment. Orthodontists benefit from accelerated tooth movement for multiple reasons pertaining to practice management and increased profitability. Orthodontists using accelerated treatment techniques have reported increased profit margins due to reduced chair time and increased organic growth due to differentiation of the practice. There are also potential negative outcomes associated with accelerated orthodontic tooth movement. For the patient, there is a potential increased risk for root resorption, increased treatment fees and pain associated with treatment. At this time, there is no published data regarding the potential for orthodontic relapse following the accelerated orthodontic tooth movement. There are several publications supporting the fact that relapse is a known risk for conventional orthodontic treatment. The investigators can make the safe assumption that accelerated orthodontic treatment would be no different than conventional orthodontic therapy with regard to relapse potential. All orthodontic patients must be compliant with regard to orthodontic retention or relapse will be expected. Most orthodontists are charging between $700-800 for AcceleDent therapy in addition to the normal orthodontic fee. Finally, there is no published data regarding pain associated with accelerated Invisalign treatment. Further, the mechanism underlying any increased orthodontic tooth movement due to vibration remains unclear. Studies on a cellular level have shown a promising but complicated mechanism of how vibration may enhance activation of various cell proliferation and differentiation molecules within the periodontal ligament (PDL) stem cells as well as increase levels of gingival inflammation biomarkers. For example, vibration therapy might accelerate breakdown of the cellular cytoskeleton, increase actinG trafficking into the nucleus, increase Runx2 gene expression, and thus facilitate bone formation. Whether this mechanotransduction mechanism can be translated into clinical tooth movement is unknown and its clinical evidence remains to be elucidated. In this study, the investigators propose a randomized prospective clinical design to investigate effects of AcceleDent vibration therapy on the efficiency of tooth movement, on the activation of gingival crevicular fluid biomarkers and on patient discomfort in conjunction with accelerated Invisalign therapy.

Official Title
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Orthodontic Tooth Movement With Accelerated Invisalign Therapy Using Acceledent Aura: A Randomized Clinical Trial

Conditions
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Malocclusion

Intervention / Treatment
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* Device: AcceleDent Aura
* Device: Accelerated Invisalign therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females over the age of 18 years old desiring orthodontic treatment. Adult dentition with all upper and lower front teeth present and any premolar and molar combination in the upper posterior of two teeth on each side. Normal pulp vitality and healthy periodontal tissues as determined by intraoral exam. Good health as determined by medical history. Willingness and ability to comply with study procedures, attend study visits, and complete the study. The ability to understand and sign a written informed consent form, which must be signed prior to initiation of study procedures. Exclusion Criteria: Patient under the age of 18 years old Women may not be pregnant. Negative urine pregnancy tests prior to exposure to cone beam imaging is required to verify pregnancy status. Patients diagnosed with systemic diseases such as diabetes, hypertension (high blood pressure), temporomandibular disorders (jaw disorders), or craniofacial syndromes. Severe malocclusions that would require adjunctive procedures other than Invisalign. These include impacted teeth, closure of extractions spaces. Significant periodontal disease (> 4mm pocket depth or >2 mm of recession on upper anterior teeth). Active caries not under care of either a dentist or periodontist. Chronic daily use of any non-steroidal anti-inflammatory medication, estrogen, calcitonin, or corticosteroids. History of use or current use of any bisphosphonate medication or other medication for treatment of osteoporosis. Current smoker (must not have smoked in the last 6 months). Failing to comply with research protocols

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Invisalign Therapy<br>Patients receiving standard Invisalign therapy will be instructed to wear each aligner 24 hours day. Patients will be permitted to progress to the subsequent aligner after 14 days of compliant aligner wear. | |
| Experimental: Accelerated Invisalign<br>Patients receiving accelerated Invisalign therapy will be instructed to wear each aligner 24 hours day. Patients will be permitted to progress to the subsequent aligner after 4 days of compliant aligner wear. | Device: Accelerated Invisalign therapy<br>* Patients receiving accelerated Invisalign therapy will be instructed to wear each aligner 24 hours day. Patients will be permitted to progress to the subsequent aligner after 4 days of compliant aligner wear.<br>|
| Experimental: Accelerated Invisalign and Vibration<br>In addition to the accelerated Invisalign protocol described in Arm #2, patients will undergo intraoral vibration therapy using an AcceleDent Aura device for a duration of 20 minutes per day. | Device: AcceleDent Aura<br>* Patients receiving vibration therapy will be instructed to bite down on the AcceleDent mouthpiece, which vibrates at a .25 Newtons (25 grams) force level with a 30 Hertz frequency for 20 minutes per day.<br>Device: Accelerated Invisalign therapy<br>* Patients receiving accelerated Invisalign therapy will be instructed to wear each aligner 24 hours day. Patients will be permitted to progress to the subsequent aligner after 4 days of compliant aligner wear.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Little's Irregularity Index (LI) at Baseline | Little's Irregularity Index is the sum of contact displacement in mm between the anterior teeth from mesial of one canine to the mesial of the contralateral canine. | Baseline (Week 0) | 
| Little's Irregularity Index at Final Stage | Little's Irregularity Index is the sum of contact displacement in mm between the anterior teeth from mesial of one canine to the mesial of the contralateral canine. | End of Study (a total of approximately 12 weeks) | 
| Rate of Orthodontic Tooth Movement [Difference in Little's Irregularity Index, mm/Day] | The rate of orthodontic tooth movement (Little's Irregularity Index mm/day) will be evaluated. Little's Irregularity Index is the sum of contact displacement in mm between the anterior teeth from mesial of one canine to the mesial of the contralateral canine. | Baseline, 12 weeks | 
| Rate of Orthodontic Tooth Movement [Total % Change of Little's Irregularity Index] | The percent change in the irregularity index between the baseline and the final will be evaluated. Little's Irregularity Index is the sum of contact displacement in mm between the anterior teeth from mesial of one canine to the mesial of the contralateral canine. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activity of Bone Turnover Markers (BTMs) During Orthodontic Tooth Movement [Quantitative Polymerase Chain Reaction (qPCR), Cycle Threshold Values (Ct)] | Gingival crevicular fluid will be sampled to determine if vibratory stimulation during orthodontic tooth movement increases the activity of the Receptor Activator of Nuclear Factor-KappaB (RANK), Receptor Activator of Nuclear Factor-KappaB Ligand (RANKL) and Osteoprotegerin (OPG) cell signaling pathway. | 12 weeks | 
| Mean Patient Discomfort Score | Research subjects asked to complete questionaire at Week 12 in order to determine what effect vibratory stimulation has on discomfort during orthodontic treatment. The FACES Pain Visual Analog Pain Scale was used to assess pain. Pain was assessed on a 0 (no pain) to 10 (worst pain) grading scale. Lower scores reflect lower pain levels. | Week 12 |