Restoring Masticatory Function to Treat Chronic Pain (MAP)

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Pain; Temporomandibular Joint Dysfunction Syndrome
• Intervention / Treatment: Procedure: Occlusal adjustment; Procedure: Placebo occlusal adjustment

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Galicia
    • Santiago de Compostela, A Coruña, Galicia, Spain, 15782
      • Universidad de Santiago de Compostela
  • A Coruña. Galicia
    • A Coruña, A Coruña. Galicia, Spain, 15006
      • Complexo Hospitalario Universitario A Coruña

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Occlusal adjustment therapy; 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; 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); Other Names: Occlusal reshaping; Selective grinding of teeth; Restoring physiological jaw-closure; Restoring impaired chewing function
Placebo Comparator: Placebo occlusal adjustment therapy; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache-intensity	Headache intensity in recent months (If any) in a 0-10 numerical pain rating scale with 0=no pain and 10= worst possible pain.	Baseline 3- and 6-Months
Number of Participants With Neuropathic Pain	Neuropathic pain Questionnaire (DN4). Over 4 scores indicates neuropathic facial pain.	Baseline, 6-Months
Handedness Preference	Handedness preference assessed using Edinburg inventory: Left Right; Writing; Drawing; Throwing; Scissors; Toothbrush; Knife (without fork); Spoon; Broom (upper hand); Striking Match (match); Opening box (lid) I Which foot do you prefer to kick with? II Which eye do you use when using only one?	Baseline
Lateral Guidance Angles (LG)	The angle between the tangent of the LG tracings and the horizontal Frankfort line, starting from the midsagittal point up 2 mm: using a calibrated Model K7 diagnostic system. Both sides recordings of each patient were measured and considered individually. The mean of both sides of each patient was not used.	Baseline
Condylar Path Angles	Parasagittal plane condylar path tracings in relation to the Frankfort Horizontal Plane following the Gysi extraoral method.	Baseline
Adverse Events	Unexpected Adverse Events (NIH, 2009).	After therapy, 1-Month, 3-Months, 6-Months
Jaw Asymmetry	Over 1 mm of interincisal midline deviation and inter-arches Angle Classification of the lateral sectors (canines and first molars); it will be assessed during maximal intercuspal position and during jaw retruded contact position	Baseline
Participant's Awareness With Trial Group Assignment	Physicians and patients are quizzed at the end of the study to determine whether or not they have guessed the therapy involved	Six months
Credibility (of Participants)	Confidence of participants in the goodness of treatment. These items were simplified here to the following single question: How confident would you be that this treatment would be successful in eliminating your pain and/or limited mouth opening? 0-10 numerical rating scale, with 0=nothing to 10= totally.	Baseline, 6-Months
Sociodemography	Level of education	Baseline
Patient Impression (Improvement)	Patient impression outcome will be reported as Improved Vs. no change.	6-Months
Pain Interference on Daily Activity	In the past 6 months, how much has facial pain interfered with your daily activities rated on a 0-10 scale where 0 is "no interference" and 10 is "unable to carry on any activities"? 0-10 VAS/NRS (0=No interference to 10=Unable to carry on any activities). N.B. Only one item was choose to simplify.	Baseline; 6-Months
Pain-dimensions	McGill Pain questionnaire	Baseline, 6-Months
Temporomandibular Disorders Related Impairment	Mandibular Function Impairment Questionnaire (MFIQ)	Baseline, 6-Mo
Circulating Biomarkers	Blood levels of Circulating Biomarkers	Baseline, 6-Months
Periodontal Disease (if Indicated)	Radiographic defect, Probing depth, Clinical attachment level, Tooth mobility Tooth mobility	Baseline, 6-Months
Occlusal Forces/Pressure	Dental or occlusal forces measured using fuji-film method.	Baseline; 6-Months
Maximum Comfortable (Without Pain) Jaw Opening	Vertical jaw-opening (incisal level) measured using a ruler.	Baseline, immediate after therapy, 3- and 6-Months
Patient's Perception of Reduced Movement	Subjective patient's perception of reduced jaw-opening; how many fingers can put between your incisors?. Higher values represent a better outcome.	Baseline, 6-Months
Protrusive Motion	Magnitude (mm) of protrusive jaw-movement (incisal level) and lateral shift (quantitative, mm; and/or qualitative, left/right), using kinesiography recordings. Higher values represent a better outcome.	Baseline, 6-Months

Collaborators and Investigators

• Sponsor: Urbano Santana Penin, MD, DDS, PhD
• Collaborators: University of Santiago de Compostela
• Investigators: Principal Investigator: Urbano Santana-Penin, Prof, University of Santiago de Compostela; Study Chair: Jose Lopez-Cedrun, Dr, University Hospital Complex of La Coruña; Study Director: Maria J Mora, Prof, University of Santiago de Compostela; Principal Investigator: Urbano Santana-Mora, Dr, University of Santiago de Compostela

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): June 15, 2018
• Study Completion (Actual): June 15, 2018

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (Estimate): May 21, 2014

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 11, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Pain; Randomized clinical trial; Therapy; Temporomandibular joint disorders; Mastication; Occlusal adjustment; Habitual chewing side; Handedness preference; Jaw asymmetry
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Stomatognathic Diseases; Jaw Diseases; Craniomandibular Disorders; Mandibular Diseases; Myofascial Pain Syndromes; Chronic Pain; Joint Diseases; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Anti-Infective Agents; Dermatologic Agents; Antifungal Agents; Keratolytic Agents; Salicylic Acid
• Other Study ID Numbers: U1111-1134-0832; ISRCTN (Registry Identifier: ISRCTN11460478); PI11/02507 (Other Grant/Funding Number: Ministry of Science and Innovation (Spain))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

A closed, certificate, database called OpenClinica allows access to members of the Data and Safety Monitoring Board.

We expect to publish raw data in Sci Data. Figures from participant's mouth could be posted in a repository. The protocol will be attached as a supplementary appendix to the main manuscript

• IPD Sharing Time Frame: The raw data of each participant, unidentifiable, will be accessible within 6 months after the publication of the manuscript and will be accessible for at least one year.
• IPD Sharing Access Criteria: Free access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF