Genetic Polymorphisms and Their Association With Temporomandibular Disorders

Recruiting

• Conditions: Orofacial Pain; Temporomandibular Disorders
• Interventions: Device: stabilization splint; Procedure: physical therapy; Device: placebo splint

• Registration Number: NCT04694274
• Lead Sponsor: Croatian Science Foundation

Brief Summary

Temporomandibular disorders (TMD) are the most common orofacial pain disorders of non-dental origin with the prevalence of 6.1-10.2%, and incidence of 3.9%. Observable pathology is mostly absent, and the etiology often remains unknown. Since some other painful conditions of unknown origin (eg. fibromyalgia), also imply genetic factors, the aim of the study is to investigate genetic predisposition in relation to the risk for TMD onset. This will be achieved through analysis of polymorphisms in the selected genes in TMD patients (DC/TMD) and matched control subjects. The possibility of involvement of specific polymorphisms in modulation of therapy response will also be investigated. The hypotheses: (I) the Single Nucleotide Polymorphism (SNPs) clustering will be dependent on presence or absence of TMD (comparison of patients with control subjects), and will possibly depend on source of pain, pain intensity, presence of bone changes, psychological features and previous orthodontic therapy, and (II) SNPs will influence the treatment response. Along with anamnestic and clinical examination and occlusal splint therapy, genomic DNA will be analyzed from the buccal swabs. Isolated DNA will be used for the determination of 19 polymorphisms of selected genes using Real-Time PCR method. The analysis of salivary oxidative stress markers and opiorphin will be also performed, as their relationship with TMD has been shown previously. This time, their concentration will be associated with polymorphisms in the promoters of genes responsible for their synthesis. The investigators expect to show that particular gene profile or group of SNPs represent a risk factor for TMD development. Innovative approach of the concept of determining the genetic predisposition for TMD has the potential for development of commercial genetic test with potential for risk estimation in relation to TMD onset. This could enable early interventions and active avoidance of environmental risk factors.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-05-01
• Study First Submitted: 2020-12-31
• Status Verified: 2021-01
• Study First Submitted QC: 2021-01-01
• Last Update Submitted: 2021-01-04
• Study First Posted: 2021-01-05
• Last Update Posted: 2021-01-06
• Primary Completion: 2024-01-30
• Study Completion: 2025-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• diagnosis of myofascial pain / arthralgia / painful disc displacement according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD)
• average pain in the last 10 days >30 mm on a Visual Analogue Scale
• pain duration of at least 3 months
• good oral hygiene
• presence of own natural teeth
• absence of any form of chronic pain in the orofacial region or in other regions of the body

Exclusion Criteria

• other orofacial pain conditions including dental pain
• poor oral hygiene, gingivitis or periodontitis
• chronic medical conditions (diabetes, cardiovascular diseases, cancer, and autoimmune diseases) - - -
• neurological and psychiatric disorders
• pregnancy
• causes of headache, unrelated to TMD, listed in the International Classification of Headache Disorders

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
group 1	physical therapy	patients with temporomandibular disorders
group 1	stabilization splint	patients with temporomandibular disorders
group 1	placebo splint	patients with temporomandibular disorders

Primary Outcome Measures

Name	Time	Method
change from baseline characteristic pain intensity at 6 months	baseline, 6th month	The characteristic pain intensity (part of Graded Chronic Pain Scale, GCPS) compute mean of items (pain right now, worst pain, average pain), and multiply by 10.; Each item ranges from 0 to 10, with higher scores mean a worse outcome.
change from baseline spontaneous pain at 6 months	baseline, 6th month	For evaluation of spontaneous pain from the temporomandibular joint and the masticatory muscles a 100 mm horizontal Visual analogue scale (VAS) is used. Visual analogue scale ranges from 0 to 100, with higher scores mean a worse outcome.

Secondary Outcome Measures

Name	Time	Method
change from baseline anxiety at 6 months	baseline, 6th month	the General anxiety disorder questionnaire (GAD-7) (a 7-question questionnaire that assesses the severity of respondents' anxiety symptoms) is used for assessing the severity of anxiety symptoms of the participants. Scale ranges fro 0 to 21, with higher scores mean a worse outcome. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively.
change from baseline depression at 6 months	baseline, 6th month	The Patient Health Questionnaire-9 (PHQ-9) is used for measuring the severity of depressive symptoms. Scores range from 0 to 27, with cut-points 5, 10, 15, and 20 represent mild, moderate, moderately severe and severe depression, respectively.
change from baseline range of mouth opening at 6 months	baseline, 6th month	1. The pain-free opening is defined as the maximum amount that a patient achieves by opening the mouth without feeling pain and is measured as the distance between the incisal edges of the upper and lower central incisors.; 2. Maximum unassisted mouth opening is measured as the distance between the maxillary and mandibular central incisors and defined as the largest amount of opening that a patient can achieve regardless of pain and discomfort.

Trial Locations

Locations (1)

School of Dental Medicine, University of Zagreb; 🇭🇷 Zagreb, N/A = Not Applicable, Croatia