Genetic Polymorphisms and Their Association With Temporomandibular Disorders

Temporomandibular Disorders Clinical Trial

— GenPolTMD  

Official title:

Genetic Polymorphisms and Their Association With Temporomandibular Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04694274
• Other study ID #: IP-2019-04-6211
• Status: Recruiting
• Start date: May 1, 2017
• Est. completion date: January 30, 2025

Study information

• Verified date: January 2021
• Source: Croatian Science Foundation
• Contact: Iva Z Alajbeg, PhD
• Phone: 0038514802125
• Email: ialajbeg[@]sfzg.hr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 30, 2025
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• Facial Pain
• Orofacial Pain
• Temporomandibular Disorders
• Temporomandibular Joint Disorders
• Temporomandibular Joint Dysfunction Syndrome

Intervention

Device:
• stabilization splint
The device made of a hard acrylic on stone cast of the upper jaw in the centric relation position. It has a thickness of 1.5 mm at the level of the first molar.

Procedure:
• physical therapy
Home-exercise program included exercises for passive and active stretching, joint mobilization, passive extension, and translational movements to the right, left, and forward.

Device:
• placebo splint
The placebo splint was made of thin heat-treatable foil (0.5 mm). The foil was heated and printed over a plaster model of the upper jaw resulting in a very thin film over the occlusal surfaces of all teeth.

Locations

Country	Name	City	State
Croatia	School of Dental Medicine, University of Zagreb	Zagreb	N/A = Not Applicable

Sponsors (1)

Lead Sponsor	Collaborator
Croatian Science Foundation

Country where clinical trial is conducted

Croatia, 

References & Publications (7)

Alajbeg IZ, Gikic M, Valentic-Peruzovic M. Mandibular Range of Movement and Pain Intensity in Patients with Anterior Disc Displacement without Reduction. Acta Stomatol Croat. 2015 Jun;49(2):119-27. doi: 10.15644/asc49/2/5. — View Citation

Alajbeg IZ, Lapic I, Rogic D, Vuletic L, Andabak Rogulj A, Illeš D, Knezovic Zlataric D, Badel T, Vrbanovic E, Alajbeg I. Within-Subject Reliability and between-Subject Variability of Oxidative Stress Markers in Saliva of Healthy Subjects: A Longitudinal Pilot Study. Dis Markers. 2017;2017:2697464. doi: 10.1155/2017/2697464. Epub 2017 Nov 15. — View Citation

Alajbeg IZ, Vrbanovic E, Lapic I, Alajbeg I, Vuletic L. Effect of occlusal splint on oxidative stress markers and psychological aspects of chronic temporomandibular pain: a randomized controlled trial. Sci Rep. 2020 Jul 3;10(1):10981. doi: 10.1038/s41598- — View Citation

Vrbanovic E, Alajbeg IZ, Alajbeg I. COVID-19 pandemic and Zagreb earthquakes as stressors in patients with temporomandibular disorders. Oral Dis. 2020 Jun 13. doi: 10.1111/odi.13488. [Epub ahead of print] — View Citation

Vrbanovic E, Alajbeg IZ, Vuletic L, Lapic I, Rogic D, Andabak Rogulj A, Illeš D, Knezovic Zlataric D, Badel T, Alajbeg I. Salivary Oxidant/Antioxidant Status in Chronic Temporomandibular Disorders Is Dependent on Source and Intensity of Pain - A Pilot Study. Front Physiol. 2018 Oct 17;9:1405. doi: 10.3389/fphys.2018.01405. eCollection 2018. — View Citation

Vrbanovic E, Alajbeg IZ. Long-term Effectiveness of Occlusal Splint Therapy Compared to Placebo in Patients with Chronic Temporomandibular Disorders. Acta Stomatol Croat. 2019 Sep;53(3):195-206. doi: 10.15644/asc53/3/1. — View Citation

Vrbanovic E, Lapic I, Rogic D, Alajbeg IZ. Changes in salivary oxidative status, salivary cortisol, and clinical symptoms in female patients with temporomandibular disorders during occlusal splint therapy: a 3-month follow up. BMC Oral Health. 2019 Jun 6;19(1):100. doi: 10.1186/s12903-019-0791-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change from baseline characteristic pain intensity at 6 months	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.	baseline, 6th month
Primary	change from baseline spontaneous pain at 6 months	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.	baseline, 6th month
Secondary	change from baseline range of mouth opening at 6 months	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.; 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.	baseline, 6th month
Secondary	change from baseline anxiety at 6 months	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.	baseline, 6th month
Secondary	change from baseline depression at 6 months	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.	baseline, 6th month