Clinical trial NCT02144233: Restoring Masticatory Function to Treat Chronic Pain
Official title: Restoring Masticatory Function as Treatment for Chronic Pain: a Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Temporomandibular Joint Dysfunction Syndrome
Chronic Pain
Keywords: Pain
Temporomandibular joint disorders
Occlusal adjustment
Therapy
Randomized clinical trial
Mastication
Habitual chewing side
Handedness preference
Jaw asymmetry
Lead sponsor: University of Santiago de Compostela
Sponsor class: OTHER
Collaborators: name: University of Santiago de Compostela
First posted: 2014-05-21
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: * 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.

Eligibility criteria: 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

Primary outcomes:
measure: Jaw-pain-Intensity (Affected Side)
timeFrame: Baseline and 6-months
Secondary outcomes:
measure: Chewing Side
timeFrame: Baseline and 6-months
measure: Change in Global Severity Index Scores (Symptom Checklist-90-Revised (SCL-90-R))
timeFrame: Baseline, 6-Months
measure: Maximum Unassisted Jaw Opening
timeFrame: Baseline, 3- and 6-Months
Other outcomes:
measure: Headache-intensity
timeFrame: Baseline 3- and 6-Months
measure: Number of Participants With Neuropathic Pain
timeFrame: Baseline, 6-Months
measure: Handedness Preference
timeFrame: Baseline
measure: Lateral Guidance Angles (LG)
timeFrame: Baseline
measure: Condylar Path Angles
timeFrame: Baseline
measure: Adverse Events
timeFrame: After therapy, 1-Month, 3-Months, 6-Months
measure: Jaw Asymmetry
timeFrame: Baseline
measure: Participant's Awareness With Trial Group Assignment
timeFrame: Six months
measure: Credibility (of Participants)
timeFrame: Baseline, 6-Months
measure: Sociodemography
timeFrame: Baseline
measure: Patient Impression (Improvement)
timeFrame: 6-Months
measure: Pain Interference on Daily Activity
timeFrame: Baseline; 6-Months
measure: Pain-dimensions
timeFrame: Baseline, 6-Months
measure: Temporomandibular Disorders Related Impairment
timeFrame: Baseline, 6-Mo
measure: Circulating Biomarkers
timeFrame: Baseline, 6-Months
measure: Periodontal Disease (if Indicated)
timeFrame: Baseline, 6-Months
measure: Occlusal Forces/Pressure
timeFrame: Baseline; 6-Months
measure: Maximum Comfortable (Without Pain) Jaw Opening
timeFrame: Baseline, immediate after therapy, 3- and 6-Months
measure: Patient's Perception of Reduced Movement
timeFrame: Baseline, 6-Months
measure: Protrusive Motion
timeFrame: Baseline, 6-Months
Locations:
city: Santiago de Compostela
country: Spain
facility: Universidad de Santiago de Compostela
state: A Coruña, Galicia
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
state: A Coruña. Galicia
Study officials:
affiliation: University of Santiago de Compostela
name: Urbano Santana-Penin, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Complex of La Coruña
name: Jose Lopez-Cedrun, Dr
role: STUDY_CHAIR
affiliation: University of Santiago de Compostela
name: Maria J Mora, Prof
role: STUDY_DIRECTOR
affiliation: University of Santiago de Compostela
name: Urbano Santana-Mora, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Santana-Mora U, Lopez-Cedrun J, Mora MJ, Otero XL, Santana-Penin U. Temporomandibular disorders: the habitual chewing side syndrome. PLoS One. 2013 Apr 8;8(4):e59980. doi: 10.1371/journal.pone.0059980. Print 2013.