Impact of Photobiomodulation on Pain During Orthodontic Treatment.

Study Overview
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Brief Summary
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The objective of this study is to determine to effect of PBM Ortho, a photobiomodulation device, in adult patients undergoing clear aligners orthodontic treatment. We hypothesize that PBM Ortho will reduced the orthodontic associated pain in the clear aligner patients. This effect will be evaluated by recording the pain on visual analog scale given to the patients before the placement of clear aligners and collecting saliva.

Detailed Description
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Pain associated with orthodontic treatment is one of the main causes of treatment discontinuation and patient non-cooperation. Several treatment modalities have been studied to alleviate orthodontic pain which includes pharmacological, mechanical, and behavioral approach. One potential treatment is the application of photobiomodulation (PBM) therapy which is a form of light therapy. The objective of this study is to determine to effect of PBM therapy in adult patients undergoing clear aligners orthodontic treatment. This effect will be evaluated by recording the pain on visual analog scale given to the patients before the placement of clear aligners and collecting saliva. The patients will be provided with active PBM Ortho device and sham PBM device (placebo, which will look similar to the active device) to use them at home for one 8 minutes application for 7 days (4 minutes per arch, upper or lower). The pain scale sheets will also be given to the patients to fill them every day for 7 days. The inflammatory protein associated with pain present in the saliva will be collected on Day 1 (24 hours after clear aligner treatment start), Day 4 (fourth day of treatment), and Day 7 (after 1 week from the treatment start). On the last visit, the device and pain scale sheets will be collected from the patients. If successful, this device therapy will reduce the orthodontic associated pain and improve patients' compliance and cooperation.

Official Title
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Impact of Photobiomodulation on Pain During Orthodontic Treatment

Conditions
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Malocclusion, Orthodontic Treatment

Intervention / Treatment
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* Device: PBM Ortho


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systemically healthy male and female patients (age 20 to 65), i.e., do not suffer from systemic illness nor require medication during the saliva collection period. Permanent dentition, with Little's Irregularity Index (LII) of 2 mm or greater for the upper and lower arch. Orthodontic treatment using clear aligners via non-extraction therapy. Patient is available for follow-up visits. Patient is able and willing to comply with the requirements of this trial protocol. Non-smoker with no use of chewing tobacco. Good oral hygiene. Caries free. No sign of periodontal disease. Exclusion Criteria: Systemic diseases Medication use for the past 6 months; specially use of anti-inflammatory (e.g., NSAIDs), antiviral, antibiotics. Smoking. Active dental caries. Any periodontal problem including bleeding, tooth mobility, bone loss, attachment loss, deep pockets. Sleep apnea and other airway pathologies.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PBM Ortho Active device<br>PBM Ortho Active group will be given an active device. | Device: PBM Ortho<br>* The device will be used by the patients at home for one 8 minutes per day (4 minutes each upper and lower) for 7 days.<br>|
| Sham Comparator: PBM Ortho Sham<br>PBM Ortho Sham device group will be given a non-active device that will not emits light. | Device: PBM Ortho<br>* The device will be used by the patients at home for one 8 minutes per day (4 minutes each upper and lower) for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 0: prior to seating first clear aligner tray | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 1 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 2 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 3 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 4 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 5 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 6 | 
| Visual analog scale | Study endpoint for effectiveness in decreasing the pain perception during orthodontic tooth movement. Pain intensity will be scored between 0 (no pain) and 10 (worst imaginable pain) on the numeric scale. Pain intensity does not have a unit to describe. The pain intensity will be recorded in both groups at Day 0 (after the placement of the first composite attachments on the teeth but before the seating of the first clear aligner), and then every day for 7 consecutive days. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Saliva analysis | 2 ml of saliva samples will be obtained from all the patients enrolled in the study at Day 0, Day 1, Day 4 and Day 7 time points in 15-ml Falcon tubes. The samples will be immediately frozen and stored at -80°C refrigerator until assayed. Multiplex immunoassay will be used to analyze target proteins: cortisol, testosterone, alpha amylase, interleukin 1β (IL-1β), prostaglandin E2 (PGE2), receptor activator of nuclear factor kappa-B ligand (RANKL), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), macrophage inflammatory protein-4 (MIP-4), matrix metalloproteinase-8 (MMP-8). ELISA kits for each target protein will be utilized to quantify the protein in the saliva and the unit will be according to the protocol provided in the kit. | The saliva will be collected on Day 0 | 
| Saliva analysis | 2 ml of saliva samples will be obtained from all the patients enrolled in the study at Day 0, Day 1, Day 4 and Day 7 time points in 15-ml Falcon tubes. The samples will be immediately frozen and stored at -80°C refrigerator until assayed. Multiplex immunoassay will be used to analyze target proteins: cortisol, testosterone, alpha amylase, interleukin 1β (IL-1β), prostaglandin E2 (PGE2), receptor activator of nuclear factor kappa-B ligand (RANKL), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), macrophage inflammatory protein-4 (MIP-4), matrix metalloproteinase-8 (MMP-8). ELISA kits for each target protein will be utilized to quantify the protein in the saliva and the unit will be according to the protocol provided in the kit. | The saliva will be collected on Day 1 | 
| Saliva analysis | 2 ml of saliva samples will be obtained from all the patients enrolled in the study at Day 0, Day 1, Day 4 and Day 7 time points in 15-ml Falcon tubes. The samples will be immediately frozen and stored at -80°C refrigerator until assayed. Multiplex immunoassay will be used to analyze target proteins: cortisol, testosterone, alpha amylase, interleukin 1β (IL-1β), prostaglandin E2 (PGE2), receptor activator of nuclear factor kappa-B ligand (RANKL), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), macrophage inflammatory protein-4 (MIP-4), matrix metalloproteinase-8 (MMP-8). ELISA kits for each target protein will be utilized to quantify the protein in the saliva and the unit will be according to the protocol provided in the kit. | The saliva will be collected on Day 4 | 
| Saliva analysis | 2 ml of saliva samples will be obtained from all the patients enrolled in the study at Day 0, Day 1, Day 4 and Day 7 time points in 15-ml Falcon tubes. The samples will be immediately frozen and stored at -80°C refrigerator until assayed. Multiplex immunoassay will be used to analyze target proteins: cortisol, testosterone, alpha amylase, interleukin 1β (IL-1β), prostaglandin E2 (PGE2), receptor activator of nuclear factor kappa-B ligand (RANKL), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), macrophage inflammatory protein-4 (MIP-4), matrix metalloproteinase-8 (MMP-8). ELISA kits for each target protein will be utilized to quantify the protein in the saliva and the unit will be according to the protocol provided in the kit. | The saliva will be collected on Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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photobiomodulation, clear aligners, orthodontic pain