Restoring Masticatory Function to Treat Chronic Pain

Study Overview
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Brief Summary
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The primary endpoint will be the average change in pain score from baseline to the three- and six-month assessments. Efficacy will be demonstrated by superior pain relief with the active treatment compared with the placebo.

Detailed Description
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The cause of temporomandibular joint (TMJ) disorders (TMD) remains unknown and therapy is usually empirical. Systematic reviews have concluded that currently there is no evidence that occlusal adjustment has any therapeutic or preventive effect on temporomandibular disorders. However, these reviews also indicate that evidence to the contrary has not been provided and that more research is needed to elucidate whether there is any benefit of occlusal adjustment treatment for TMD. The risk factors for chronic unilateral TMD include a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the affected side. Consequently, a new occlusal therapy is proposed to restore the physiological jaw closure and masticatory function. The primary end point of the trial is to assess the efficacy of the new occlusal therapy on the affected side TMD pain, and the maximum mouth opening. Efficacy is demonstrated by showing significantly superior pain relief and increasing maximum mouth opening (when it was limited) with the active treatment compared with placebo. Phase III, single center, randomized, parallel-group, single-blind with blinded assessment, placebo-controlled clinical trial. A linear mixed model will be performed for comparisons of most variables and a logistic regression model will be used to measure the probability/risk of change on the chewing side between baseline and six months; in addition, McNemar's test may be used. Interim analysis plan and stopping rules. The study will employ an interim analysis plan with a single interim analysis after 70% of participants have completed the six-month follow-up visit. Using the Lan-DeMets version of the O'Brien-Fleming stopping rule, the critical value for statistical significance at the interim analysis (under intention-to-treat approach) will be +2.438, corresponding to a nominal two-sided P value of 0.0146. Participants remaining with significant pain (and/or limited mouth opening) after the study will be invited to follow the conventional treatment, or to complete occlusal adjustment (rescue therapy): the full adjustment (if they were placebos), or a refining (if they received real therapy); the kind of received therapy will not be disclosed to participants. It based on the researchers' conviction, participants are encouraged to receive electively complete occlusal adjustment. All participants will be reevaluated between 3 to 6 months after study (12-Mo follow-up). Although no pain was reported at the 6-Mo follow-up, if pain returns, same approach will be carried out. Two sessions occlusal adjustment will be carried out and, if the pain remains, the patient will be treated following the Hospital approaches. The evolution of patients during post-MAP period, until writing of the manuscript, will be reported in the same manuscript, even if MAP result early stopped. Additional patient's monitoring until next five years after treatment is expected.

Official Title
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Restoring Masticatory Function as Treatment for Chronic Pain: a Randomized Placebo-controlled Trial

Conditions
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Temporomandibular Joint Dysfunction Syndrome, Chronic Pain

Intervention / Treatment
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* Procedure: Occlusal adjustment
* Procedure: Placebo occlusal adjustment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completely dentate (except for the third molars; including if they were treated before enrollment by conventional or implant-supported fixed prosthesis allowing similar potential comfortable chewing on both sides) Normal Angle Class I occlusion Self-reported pain-intensity scores from 4 to 9 in a 0-10 visual analogue scale (VAS) or numerical pain rating scale (NRS). Chronic (over 6 months) joint and/or muscle pain, according to diagnostic criteria for temporomandibular disorders (DC/TMD), for which they had requested therapy Exclusion Criteria: Psychosis Major depression Substance abuse Cognitive impairment Addiction to morphine or derivates Litigation or asking for disability/retirement compensation for chronic pain Dental care professionals Orthodontic therapy during the last 2 years Patients with any pain that is more severe, in the same location as, or cannot be clearly distinguished from TMD pain Individuals for whom minimally invasive occlusal adjustment could not achieve occlusal equilibration, including: Over 2 mm of difference between the maximal intercuspal position and the centric occlusion or over 4 mm of difference between upper and lower archs (or over 2mm on at less one side) measured: between the mesial fosses of first upper premolars with respect the buccal cusps of the first lower premolars; and/or between the mesiopalatal cusp of the first upper molars respect to the central (mesial) fossae of the first lower molar. Severe periodontal disease with grade 3 mobility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Occlusal adjustment therapy<br>Occlusal adjustment therapy consists of the elimination of premature tooth contacts during retruded jaw closure, and the reduction of the steeper lateral anterior guidance; the magnitude of this alteration will be estimated by the following equation: (right condylar path) × (left anterior guidance) = (left condylar path) × (right anterior guidance). A resin-composite, placed mainly in the canine tooth, can be used to increases the flatter lateral guidance on the habitual chewing side; overcorrection is expected to compensate for a masticatory preference on the opposite side to the handedness. | Procedure: Occlusal adjustment<br>* The first step consists of the elimination of premature tooth contacts during retruded jaw closure. The second step included reduction of the steeper lateral anterior guidance; the magnitude of this alteration will be estimated by the following equation: (right condylar path) × (left anterior guidance) = (left condylar path) × (right anterior guidance)<br>* Other names: Restoring impaired chewing function;|
| Placebo Comparator: Placebo occlusal adjustment therapy<br>Placebo occlusal adjustment will take place in a manner identical to the real adjustment. However, a specially fabricated inactive rotary instrument will be used, and no enamel will be removed. | Procedure: Placebo occlusal adjustment<br>* Placebo occlusal adjustment will take place in a manner identical to the real adjustment. However, a specially fabricated inactive rotary instrument will be used, and no enamel will be removed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jaw-pain-Intensity (Affected Side) | Self-reported affected-side pain-intensity across the trial in a 0-10 visual analogue scale (VAS) (0=no pain, 10=worst possible pain). Higher values represent a worse outcome. | Baseline and 6-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chewing Side | A consistent chewing side was considered if at lees 5 out of 7 almonds (or at lees 7 of 10 cycles of chewing gum), the participant report to use same side, and same side was used during kinesiography recordings of spontaneous chewing. Any other results lead to alternate chewing allocation. | Baseline and 6-months | 
| Change in Global Severity Index Scores (Symptom Checklist-90-Revised (SCL-90-R)) | Mean change in Global Severity Index scores from a self-administered Spanish validated questionaire SCL-90-R. Higher values represent a worse outcome. Range (0-4). | Baseline, 6-Months | 
| Maximum Unassisted Jaw Opening | Vertical jaw-opening (incisal level) measured using a ruler. Higher values represent a better outcome. | Baseline, 3- and 6-Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Temporomandibular joint disorders, Occlusal adjustment, Therapy, Randomized clinical trial, Mastication, Habitual chewing side, Handedness preference, Jaw asymmetry